Parthanatos, a messenger of death

David, Karen Kate

doi:10.2741/3297

Cited by 451Cell death mechanisms and regulationPARP inhibition in cancer therapyDNA Repair Mechanisms

Parthanatos, a messenger of death

Open access

David, Karen Kate·2009·Frontiers in Bioscience

DOI 10.2741/3297PMC PMC4450718

Open this paper in CoChat — free account Open PDF

Abstract

Poly-ADP-ribose polymerase-1 (PARP-1)'s roles in the cell span from maintaining life to inducing death. The processes PARP-1 is involved in include DNA repair, DNA transcription, mitosis, and cell death. Of PARP-1's different cellular functions, its role in cell death is of particular interest to designing therapies for diseases. Genetic deletion of PARP-1 revealed that PARP-1 overactivation underlies cell death in models of stroke, diabetes, inflammation and neurodegeneration. Since interfering with PARP-1 mediated cell death will be clinically beneficial, great effort has been invested into understanding mechanisms downstream of PARP-1 overactivation. Recent evidence shows that poly-ADP ribose (PAR) polymer itself can act as a cell death effector downstream of PARP-1. We coined the term parthanatos after Thanatos, the personification of death in Greek mythology, to refer to PAR-mediated cell death. In this review, we will present evidence and questions raised by these recent findings, and summarize the proposed mechanisms by which PARP-1 overactivation kills. It is evident that further understanding of parthanatos opens up new avenues for therapy in ameliorating diseases related to PARP-1 overactivation.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.2741/3297

Cites

96 of 96 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Parthanatos occurs not only as a consequence of severe/prolonged alkylating DNA damage, but also in response to oxidative stress, hypoxia, hypoglycemia, or inflammatory cues.
“parthanatos appears to occur not only as a consequence of severe/prolonged alkylating DNA damage, but also in response to oxidative stress, hypoxia, hypoglycemia, or inflammatory cues [656–658].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [658]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Control of inositol 1,4,5-trisphosphate-induced Ca2+ release by cytosolic Ca2+
Bootman, M. D., Missiaen, L., Parys, J. B., SMEDT, H. D., & Casteels, R. (1995) · Biochemical Journal · doi:10.1042/bj3060445 · Cited by 5,120 · see citing works
Molecular characterization of mitochondrial apoptosis-inducing factor
Susin, S. A., Lorenzo, H. K., Zamzami, N., Marzo, I., Snow, B. E., Brothers, G. M., Mangion, J., Jacotot, E., Costantini, P., Loeffler, M., et al. (1999) · Nature · doi:10.1038/17135 · Cited by 4,060 · cited 3× · see citing works
“Translocation of AIF to the nucleus induces chromatin condensation and DNA fragmentation possibly through cyclophilin A, even in the presence of caspase inhibitors (48, 49, 54, 61).”
Background
Mitochondrial membrane permeabilization in cell death
Kroemer, G., Galluzzi, L., & Brenner, C. (2007) · Physiological Reviews · doi:10.1152/physrev.00013.2006 · Cited by 3,598 · cited 13× · see citing works
“Mandir AS, Przedborski S, Jackson-Lewis V, Wang ZQ, Simbulan-Rosenthal CM, Smulson ME, Hoffman BE, Guastella DB, Dawson VL, Dawson TM. Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6- tetrahydropyridine (MPTP)-induced parkinsonism.”
BackgroundInfluential
Excitatory Amino Acids as a Final Common Pathway for Neurologic Disorders
Epstein, F. H., Lipton, S. A., & Rosenberg, P. A. (1994) · New England Journal of Medicine · doi:10.1056/nejm199403033300907 · Cited by 2,644 · cited 2× · see citing works
“Neuronal damage following ischemia is known to be mediated by overactivation of N-methyl-D-aspartic acid (NMDA) glutamate receptors due to excess glutamate released by injured neurons (13).”
Background
Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death
Baines, C. P., Kaiser, R. A., Purcell, N. H., Blair, N. S., Osinska, H., Hambleton, M. A., Brunskill, E. W., Sayen, M. R., Gottlieb, R. A., Dorn, G. W., et al. (2005) · Nature · doi:10.1038/nature03434 · Cited by 2,280 · cited 1× · see citing works
“Moreover, mice lacking cyclophilin D are protected against ischemia-reperfusion injury (88-90).”
Background
Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures.
Dawson, V. L., Dawson, T. M., London, E. D., Bredt, D. S., & Snyder, S. H. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.14.6368 · Cited by 2,174 · cited 2× · see citing works
“Excess NO by reacting with superoxide anion to produce the oxidant peroxynitrite causes DNA damage that activates PARP-1 (15, 22, 23).”
Background
Peroxynitrite: biochemistry, pathophysiology and development of therapeutics
Szabó, C., Ischiropoulos, H., & Radi, R. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2222 · Cited by 2,134 · see citing works
Poly(ADP-ribose): novel functions for an old molecule
Schreiber, V., Dantzer, F., Amé, J., & de MURCIA, G. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1963 · Cited by 1,917 · cited 4× · see citing works
“With this approach, 17 PARP family members have been identified that can potentially carry out poly-ADP ribosylation activities (5).”
BackgroundMethodInfluential
Mediation of Poly(ADP-Ribose) Polymerase-1-Dependent Cell Death by Apoptosis-Inducing Factor
Yu, S.-W., Wang, H., Poitras, M. F., Coombs, C., Bowers, W. J., Federoff, H. J., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2002) · Science · doi:10.1126/science.1072221 · Cited by 1,826 · cited 6× · see citing works
“This nuclear apoptosis can be blocked by microinjecting neutralizing antibodies against AIF into the cytosol (32, 49), inhibition of cysteine proteases (62) and overexpression of hsp70 (63, 64).”
BackgroundInfluential
Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions
D’Amours, D., Desnoyers, S., D’Silva, I., & Poirier, G. G. (1999) · Biochemical Journal · doi:10.1042/bj3420249 · Cited by 1,819 · cited 6× · see citing works
“Its substrates include, but are not limited to histones, DNA helicases, high mobility group proteins, topoisomerases I and II, single-strand break repair factors, baseexcision repair factors and several transcription factors (reviewed in (2)).”
BackgroundInfluential
Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death
Nakagawa, T., Shimizu, S., Watanabe, T., Yamaguchi, O., Otsu, K., Yamagata, H., Inohara, H., Kubo, T., & Tsujimoto, Y. (2005) · Nature · doi:10.1038/nature03317 · Cited by 1,635 · cited 1× · see citing works
“Moreover, mice lacking cyclophilin D are protected against ischemia-reperfusion injury (88-90).”
Background
Effects of Cerebral Ischemia in Mice Deficient in Neuronal Nitric Oxide Synthase
Huang, Z., Huang, P. L., Panahian, N., Dalkara, T., Fishman, M. C., & Moskowitz, M. A. (1994) · Science · doi:10.1126/science.7522345 · Cited by 1,562 · cited 15× · see citing works
“When accumulation of PAR polymer is antagonized by immunodepletion using antiserum to PAR or when PAR polymer is degraded through PARG overexpression, cell death is decreased in both NMDA treated neurons and MNNG treated Hela cells (33, 34).”
BackgroundInfluential
The PARP superfamily
Amé, J., Spenlehauer, C., & de MURCIA, G. (2004) · BioEssays · doi:10.1002/bies.20085 · Cited by 1,463 · see citing works
The Therapeutic Potential of Poly(ADP-Ribose) Polymerase Inhibitors
Virág, L., & Szabó, C. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.3.375 · Cited by 1,373 · see citing works
Essential role of the mitochondrial apoptosis-inducing factor in programmed cell death
Joza, N. A., Susín, S. A., Daugas, É., Stanford, W. L., Cho, S. K., Li, C. Y. J., Sasaki, T., Elia, A., Cheng, H.-Y. M., Ravagnan, L., et al. (2001) · Nature · doi:10.1038/35069004 · Cited by 1,365 · cited 2× · see citing works
“Translocation of AIF to the nucleus induces chromatin condensation and DNA fragmentation possibly through cyclophilin A, even in the presence of caspase inhibitors (48, 49, 54, 61).”
Background
Bcl-2 inhibits the mitochondrial release of an apoptogenic protease.
Susín, S. A., Zamzami, N., Castedo, M., Hirsch, T., Marchetti, P., Macho, A., Daugas, É., Geuskens, M., & Kroemer, G. (1996) · The Journal of Experimental Medicine · doi:10.1084/jem.184.4.1331 · Cited by 1,133 · cited 1× · see citing works
“AIF was purified from supernatants of mitochondria induced to undergo permeability transition (46).”
Method
Nitric Oxide Activation of Poly(ADP-Ribose) Synthetase in Neurotoxicity
Zhang, J., Dawson, V. L., Dawson, T. M., & Snyder, S. H. (1994) · Science · doi:10.1126/science.8080500 · Cited by 1,118 · cited 2× · see citing works
“PARP-1 activation plays a prominent role in NMDA excitotoxicity as PARP inhibitors protect neurons from NMDA excitoxicity and NO-mediated toxicity (21, 24, 25).”
Background
Poly(ADP-ribose) polymerase gene disruption renders mice resistant to cerebral ischemia
Eliasson, M. J. L., Sampei, K., Mandir, A. S., Hurn, P. D., Traystman, R. J., Bao, J., Pieper, A. A., Wang, Z., Dawson, T. M., Snyder, S. H., et al. (1997) · Nature Medicine · doi:10.1038/nm1097-1089 · Cited by 1,019 · cited 2× · see citing works
“Furthermore, PARP-1 KO mice are profoundly resistant to stroke and NMDA excitotoxicity (24-26).”
Background
Mechanisms of nitric oxide-mediated neurotoxicity in primary brain cultures
Dawson, V., Dawson, T., Bartley, D., Uhl, G. R., & Snyder, S. H. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-06-02651.1993 · Cited by 1,014 · cited 1× · see citing works
“nNOS plays an important role in excitotoxicity since primary brain cultures obtained from nNOS KO mice or wild type cultures treated with NOS inhibitors are resistant to NMDA excitotoxicity (15-19).”
Background
Nutrient-Sensitive Mitochondrial NAD+ Levels Dictate Cell Survival
Yang, H., Yang, T., Baur, J. A., Perez, E., Matsui, T., Carmona, J. J., Lamming, D. W., Souza-Pinto, N. C., Bohr, V. A., Rosenzweig, A., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.035 · Cited by 950 · cited 2× · see citing works
“Thus, conclusions made from these studies need to be reexamined in light of the recent finding that the mitochondrial levels of NAD+ remain at physiological levels following genotoxic stress and can support viability even when nuclear and cytoplasmic pools of NAD+ are depleted (42).”
Background
Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors
Jagtap, P. G., & Szabó, C. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1718 · Cited by 896 · see citing works
Heat-shock protein 70 antagonizes apoptosis-inducing factor
Ravagnan, L., Gurbuxani, S. K., Susín, S. A., Maisse, C., Daugas, É., Zamzami, N., Mak, T. W., Jäättelä, M., Penninger, J. M., Garrido, C., et al. (2001) · Nature Cell Biology · doi:10.1038/ncb0901-839 · Cited by 859 · cited 1× · see citing works
“This nuclear apoptosis can be blocked by microinjecting neutralizing antibodies against AIF into the cytosol (32, 49), inhibition of cysteine proteases (62) and overexpression of hsp70 (63, 64).”
Background
Cyclophilin D is a component of mitochondrial permeability transition and mediates neuronal cell death after focal cerebral ischemia
Schinzel, A. C., Takeuchi, O., Huang, Z., Fisher, J. K., Zhou, Z., Rubens, J., Hetz, C., Danial, N. N., Moskowitz, M. A., & Korsmeyer, S. J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505294102 · Cited by 820 · cited 1× · see citing works
“Moreover, mice lacking cyclophilin D are protected against ischemia-reperfusion injury (88-90).”
Background
Poly(ADP-Ribose) in the Cellular Response to DNA Damage
Berger, N. A. (1985) · Radiation Research · doi:10.2307/3576299 · Cited by 777 · cited 2× · see citing works
“Since PARP-1 consumes NAD+, Berger and colleagues postulated that PARP-1 overactivation leads to massive consumption of NAD+, followed by ATP depletion (30).”
Background
Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death
Yu, S.-W., Andrabi, S. A., Wang, H., Kim, N. S., Poirier, G. G., Dawson, T. M., & Dawson, V. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606528103 · Cited by 718 · see citing works
Nitric oxide synthase generates superoxide and nitric oxide in arginine-depleted cells leading to peroxynitrite-mediated cellular injury.
Xia, Y., Dawson, V. L., Dawson, T. M., Snyder, S. H., & Zweier, J. L. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6770 · Cited by 718 · cited 1× · see citing works
“Excess NO by reacting with superoxide anion to produce the oxidant peroxynitrite causes DNA damage that activates PARP-1 (15, 22, 23).”
Background
Role of poly(ADP-ribose) synthetase in inflammation and ischaemia–reperfusion
Szabó, C., & Dawson, V. L. (1998) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(98)01193-6 · Cited by 685 · see citing works
Nuclear ADP-Ribosylation Reactions in Mammalian Cells: Where Are We Today and Where Are We Going?
Hassa, P. O., Haenni, S. S., Elser, M., & Hottiger, M. O. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00040-05 · Cited by 682 · cited 10× · see citing works
“PARG and the recently identified ARH3 degrade PAR polymers (1, 74).”
BackgroundInfluential
Pathological implications of nitric oxide, superoxide and peroxynitrite formation
Beckman, J. S., & Crow, J. P. (1993) · Biochemical Society Transactions · doi:10.1042/bst0210330 · Cited by 676 · cited 1× · see citing works
“Excess NO by reacting with superoxide anion to produce the oxidant peroxynitrite causes DNA damage that activates PARP-1 (15, 22, 23).”
Background
The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet
Loo, G., Saelens, X., van Gurp, M., MacFarlane, M., Martin, S. J., & Vandenabeele, P. (2002) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401088 · Cited by 665 · cited 1× · see citing works
“formation (60), the mechanism by which AIF kills is not clear.”
Background
Nicotinamide mononucleotide activation of a new DNA-dependent polyadenylic acid synthesizing nuclear enzyme
Chambon, P., Weill, J. D., & Mandel, P. (1963) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(63)90024-x · Cited by 654 · cited 1× · see citing works
“(7) as nicotinamide mononucleotide (NMD)-induced and involving DNA-dependent incorporation of ATP into a nuclear extract with poly-adenine as the possible product.”
Background
Poly(ADP-ribose) (PAR) polymer is a death signal
Andrabi, S. A., Kim, N. S., Yu, S.-W., Wang, H., Koh, D. W., Sasaki, M., Klaus, J. A., Otsuka, T., Zhang, Z., Koehler, R. C., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606526103 · Cited by 644 · cited 10× · see citing works
“When accumulation of PAR polymer is antagonized by immunodepletion using antiserum to PAR or when PAR polymer is degraded through PARG overexpression, cell death is decreased in both NMDA treated neurons and MNNG treated Hela cells (33, 34).”
BackgroundInfluential
Functional interaction between PARP‐1 and PARP‐2 in chromosome stability and embryonic development in mouse
Murcia, J. M., Ricoul, M., Tartier, L., Niedergang, C., Huber, A., Dantzer, F., Schreiber, V., Amé, J., Dierich, A., LeMeur, M., et al. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg206 · Cited by 629 · cited 1× · see citing works
“Mice lacking PARP-1 or PARP-2 are viable, but mice lacking both PARPs are embryonic lethal (78).”
Background
Ischemic Brain Injury is Mediated by the Activation of Poly(ADP-Ribose)Polymerase
Endres, M., Wang, Z., Namura, S., Waeber, C., & Moskowitz, M. A. (1997) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199711000-00002 · Cited by 622 · cited 2× · see citing works
“Furthermore, PARP-1 KO mice are profoundly resistant to stroke and NMDA excitotoxicity (24-26).”
Background
AIF deficiency compromises oxidative phosphorylation
Vahsen, N., Candé, C., Brière, J.-J., Bénit, P., Joza, N. A., Larochette, N., Mastroberardino, P. G., Péquignot, M. O., Casares, N., Lazar, V., et al. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600461 · Cited by 622 · cited 2× · see citing works
“Analysis of recombinant AIF reveals NADH-oxidase activity that can catalyze formation of superoxide anions (53) further suggesting a role for AIF in redox processes within the mitochondria.”
Background
Neurotoxicity of excitatory amino acids
Guidotti, A. (1990) · Raven Press eBooks · Cited by 619 · see citing works
The harlequin mouse mutation downregulates apoptosis-inducing factor
Klein, J. A., Longo-Guess, C. M., Rossmann, M. P., Seburn, K. L., Hurd, R. E., Frankel, W. N., Bronson, R. T., & Ackerman, S. L. (2002) · Nature · doi:10.1038/nature01034 · Cited by 605 · cited 2× · see citing works
“proviral insertion in the AIF gene that results in an 80% reduction of AIF protein levels (55).”
Background
The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases
Paul, O. H. (2007) · Frontiers in bioscience · doi:10.2741/2909 · Cited by 587 · cited 3× · see citing works
“Hassa PO, Haenni SS, Elser M, Hottiger MO. Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going?”
Method
Poly(ADP-ribose) Binds to Specific Domains in DNA Damage Checkpoint Proteins
Pleschke, J. M., Kleczkowska, H. E., Strohm, M., & Althaus, F. R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m006520200 · Cited by 536 · cited 1× · see citing works
“PAR binding is selective depending on the PAR chain length and the presence of binding sites on the substrates (1, 81-83).”
Background
Poly(ADP-ribose) polymerase-1: what have we learned from the deficient mouse model?
Shall, S., & de MURCIA, G. (2000) · Mutation Research/DNA Repair · doi:10.1016/s0921-8777(00)00016-1 · Cited by 534 · cited 3× · see citing works
“Interestingly, knocking out PARP-1 alone is sufficient to protect completely from endotoxic and excitotoxic stimuli (12), whereas knocking out PARP-2 protects from focal David et al.”
BackgroundMethodInfluential
The Adenine Nucleotide Translocase: A Central Component of the Mitochondrial Permeability Transition Pore and Key Player in Cell Death
Halestrap, A. P., & Brenner, C. (2003) · Current Medicinal Chemistry · doi:10.2174/0929867033457278 · Cited by 505 · cited 1× · see citing works
“PTP can be inhibited by the immunophilin cyclosporin A (85) or bongkrekic acid (86).”
Background
Apoptosis‐inducing factor (AIF): a ubiquitous mitochondrial oxidoreductase involved in apoptosis
Daugas, É., Nochy, D., Ravagnan, L., Loeffler, M. W., Susín, S. A., Zamzami, N., & Kroemer, G. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)01731-2 · Cited by 467 · cited 1× · see citing works
“This ubiquitously-expressed mitochondrial protein was isolated for its ability to induce nuclear fragmentation, and was shown to translocate from the mitochondria to the nucleus to induce chromatin condensation and DNA fragmentation (47).”
Background
Calpain I Induces Cleavage and Release of Apoptosis-inducing Factor from Isolated Mitochondria
Polster, B. M., Basáñez, G., Etxebarria, A., Hardwick, J. M., & Nicholls, D. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m413269200 · Cited by 438 · see citing works
Cyclosporin A binding to mitochondrial cyclophilin inhibits the permeability transition pore and protects hearts from ischaemia/reperfusion injury
Halestrap, A. P., Connern, C. P., Griffiths, E. J., & Kerr, P. M. (1997) · Springer eBooks · doi:10.1007/978-1-4615-6111-8_25 · Cited by 421 · see citing works
Mechanisms of AIF-Mediated Apoptotic DNA Degradation in <i>Caenorhabditis elegans</i>
Wang, X., Yang, C., Chai, J., Shi, Y., & Xue, D. (2002) · Science · doi:10.1126/science.1076194 · Cited by 393 · cited 1× · see citing works
“Translocation of AIF to the nucleus induces chromatin condensation and DNA fragmentation possibly through cyclophilin A, even in the presence of caspase inhibitors (48, 49, 54, 61).”
Background
Poly(ADP-ribose) Polymerase-1-dependent Cardiac Myocyte Cell Death during Heart Failure Is Mediated by NAD+ Depletion and Reduced Sir2α Deacetylase Activity
Pillai, J. B., Isbatan, A., Imai, S., & Gupta, M. P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506162200 · Cited by 391 · see citing works
NADH Oxidase Activity of Mitochondrial Apoptosis-inducing Factor
Miramar, M. D., Costantini, P., Ravagnan, L., Saraiva, L. M., Haouzi, D., Brothers, G. M., Penninger, J. M., Peleato, M. L., Kroemer, G., & Susín, S. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010498200 · Cited by 388 · cited 1× · see citing works
“Later studies point that this increased levels of reactive oxygen radicals in Hq mice may be due to a role for AIF in the complex I activity of the electron transport chain (53, 58).”
Background
Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism
Mandir, A. S., Przedborski, S., Jackson-Lewis, V., Wang, Z.-Q., Simbulan-Rosenthal, C. M., Smulson, M. E., Hoffman, B. E., Guastella, D. B., Dawson, V. L., & Dawson, T. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5774 · Cited by 382 · cited 6× · see citing works
“Mandir AS, Przedborski S, Jackson-Lewis V, Wang ZQ, Simbulan-Rosenthal CM, Smulson ME, Hoffman BE, Guastella DB, Dawson VL, Dawson TM. Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6- tetrahydropyridine (MPTP)-induced parkinsonism.”
BackgroundInfluential
Poly(ADP-ribose) Polymerase-1-mediated Cell Death in Astrocytes Requires NAD+ Depletion and Mitochondrial Permeability Transition
Alano, C. C., Ying, W., & Swanson, R. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313329200 · Cited by 374 · cited 2× · see citing works
“In addition, blocking PTP by cyclosporin A can preserve mitochondrial NAD+ pools (87).”
Background
Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space
Otera, H., Ohsakaya, S., Nagaura, Z.-I., Ishihara, N., & Mihara, K. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600614 · Cited by 357 · cited 1× · see citing works
“However, recent studies indicate that it is processed to a 62-kDa form upon cleavage of its mitochondrial localization sequence, and it is only processed to the 57-kDa form after a cell death stimulus (50, 51).”
Background
On the formation of a novel adenylic compound by enzymatic extracts of liver nuclei
Chambon, P., Weill, J., Doly, J., Strosser, M. T., & Mandel, P. (1966) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(66)90502-x · Cited by 345 · cited 1× · see citing works
“Further analysis revealed that poly-ADP ribose, not poly-adenine, is the product of the reaction (8-11).”
Background
Failure to degrade poly(ADP-ribose) causes increased sensitivity to cytotoxicity and early embryonic lethality
Koh, D. W., Lawler, A. M., Poitras, M. F., Sasaki, M., Wattler, S., Nehls, M. C., Stöger, T., Poirier, G. G., Dawson, V. L., & Dawson, T. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406182101 · Cited by 339 · cited 3× · see citing works
“5 (76), suggesting that PARG is essential for survival (5).”
Background
Apoptosis-Inducing Factor Triggered by Poly(ADP-Ribose) Polymerase and Bid Mediates Neuronal Cell Death after Oxygen-Glucose Deprivation and Focal Cerebral Ischemia
Culmsee, C., Zhu, C., Landshamer, S., Becattini, B., Wagner, E., Pellecchia, M., Blomgren, K., & Plesnila, N. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2818-05.2005 · Cited by 339 · cited 2× · see citing works
“AIF is a key in neuronal cell death paradigms, since mice with reduced levels of AIF through siRNA or through the Hq mutation have reduced levels of AIF have decreased infarct size after ischemic injury (51, 56, 65).”
Background
Sequential Activation of Poly(ADP-Ribose) Polymerase 1, Calpains, and Bax Is Essential in Apoptosis-Inducing Factor-Mediated Programmed Necrosis
Moubarak, R. S., Yuste, V. J., Artus, C., Bouharrour, A., Greer, P. A., Murcia, J. M., & Susín, S. A. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.02141-06 · Cited by 322 · cited 10× · see citing works
“Downstream of PARP-1 overactivation and complex PAR accumulation, PAR migrates from the nuclei to the cytosol, leading to AIF translocation from the mitochondria to the nucleus (33, 34, 45).”
BackgroundInfluential
Studies on the Polymer of Adenosine Diphosphate Ribose
Nishizuka, Y., Ueda, K., Nakazawa, K., & Hayaishi, O. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)95947-8 · Cited by 309 · cited 3× · see citing works
“Further analysis revealed that poly-ADP ribose, not poly-adenine, is the product of the reaction (8-11).”
Background
Critical Role of Calpain I in Mitochondrial Release of Apoptosis-Inducing Factor in Ischemic Neuronal Injury
Cao, G., Xing, J., Xiao, X., Liou, A. K. F., Gao, Y., Yin, X., Clark, R. S. B., Graham, S. H., & Chen, J. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2826-07.2007 · Cited by 304 · cited 4× · see citing works
“However, recent studies indicate that it is processed to a 62-kDa form upon cleavage of its mitochondrial localization sequence, and it is only processed to the 57-kDa form after a cell death stimulus (50, 51).”
BackgroundInfluential
Identification and Characterization of a Mammalian 39-kDa Poly(ADP-ribose) Glycohydrolase
Oka, S., Kato, J., & Moss, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m510290200 · Cited by 290 · see citing works
Involvement of apoptosis‐inducing factor in neuronal death after hypoxia‐ischemia in the neonatal rat brain
Zhu, C., Qiu, L., Wang, X., Hallin, U., Candé, C., Kroemer, G., Hagberg, H., & Blomgren, K. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01832.x · Cited by 288 · cited 1× · see citing works
“AIF translocation to the nucleus has been observed in different cell types induced to die, including a myriad of cases of neuronal cell death (65), experimental models of Parkinson's disease (66), excitotoxicity (67), perinatal hypoxia-ischemia (68, 69), brain trauma (70), and ischemic stroke (65, 71-73).”
Background
Blockade of neuronal nitric oxide synthase protects against excitotoxicity in vivo
Schulz, J. B., Matthews, R., Jenkins, B. G., Ferrante, R. J., Siwek, D. F., Henshaw, D. R., Cipolloni, P. B., Mecocci, P., Kowall, N. W., & Rosen, B. R. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-12-08419.1995 · Cited by 281 · cited 1× · see citing works
“nNOS plays an important role in excitotoxicity since primary brain cultures obtained from nNOS KO mice or wild type cultures treated with NOS inhibitors are resistant to NMDA excitotoxicity (15-19).”
Background
Intranuclear localization of apoptosis‐inducing factor (AIF) and large scale dna fragmentation after traumatic brain injury in rats and in neuronal cultures exposed to peroxynitrite
Zhang, X., Chen, J., Graham, S. H., Du, L., Kochanek, P. M., Draviam, R. A., Guo, F., Nathaniel, P. D., Szabó, C., Watkins, S. C., et al. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00975.x · Cited by 254 · cited 1× · see citing works
“AIF translocation to the nucleus has been observed in different cell types induced to die, including a myriad of cases of neuronal cell death (65), experimental models of Parkinson's disease (66), excitotoxicity (67), perinatal hypoxia-ischemia (68, 69), brain trauma (70), and ischemic stroke (65, 71-73).”
Background
Structure of the catalytic fragment of poly(AD-ribose) polymerase from chicken.
Ruf, A., Murcia, J. M., de MURCIA, G., & Schulz, G. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.15.7481 · Cited by 243 · cited 1× · see citing works
“The crystal structure of the catalytic domain of chicken PARP-1 shows structural homology with the active site of bacterial ADP-ribosylating toxins (3).”
Background
Dominant cell death induction by extramitochondrially targeted apoptosis‐inducing factor
Loeffler, M. W., Daugas, É., Susín, S. A., Zamzami, N., Métivier, D., Nieminen, A., Brothers, G. M., Penninger, J. M., & Kroemer, G. (2001) · The FASEB Journal · doi:10.1096/fj.00-0388com · Cited by 241 · cited 2× · see citing works
“Translocation of AIF to the nucleus induces chromatin condensation and DNA fragmentation possibly through cyclophilin A, even in the presence of caspase inhibitors (48, 49, 54, 61).”
Background
NMDA But Not Non-NMDA Excitotoxicity is Mediated by Poly(ADP-Ribose) Polymerase
Mandir, A. S., Poitras, M. F., Berliner, A. R., Herring, W. J., Guastella, D. B., Feldman, A. B., Poirier, G. G., Wang, Z., Dawson, T. M., & Dawson, V. L. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-21-08005.2000 · Cited by 213 · see citing works
Apoptosis-inducing factor is a major contributor to neuronal loss induced by neonatal cerebral hypoxia-ischemia
Zhu, C., Wang, X., Huang, Z., Qiu, L., Xu, F., Vahsen, N., Nilsson, M., Eriksson, P. S., Hagberg, H., Culmsee, C., et al. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4402053 · Cited by 213 · cited 1× · see citing works
“AIF is a key in neuronal cell death paradigms, since mice with reduced levels of AIF through siRNA or through the Hq mutation have reduced levels of AIF have decreased infarct size after ischemic injury (51, 56, 65).”
Background
Muscle-Specific Loss of Apoptosis-Inducing Factor Leads to Mitochondrial Dysfunction, Skeletal Muscle Atrophy, and Dilated Cardiomyopathy
Joza, N. A., Oudit, G. Y., Brown, D., Bénit, P., Kassiri, Z., Vahsen, N., Benoît, L. A., Patel, M. M., Nowikovsky, K., Vassault, A. J., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.23.10261-10272.2005 · Cited by 206 · cited 2× · see citing works
“These mice develop a late-onset degeneration in the cerebellar granule cells and retinal ganglion cells (57).”
Background
Loss of poly(ADP-ribose) glycohydrolase causes progressive neurodegeneration in Drosophila melanogaster
Hanai, S., Kanai, M., Ohashi, S., Okamoto, K., Yamada, M., Takahashi, H., & Miwa, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2237114100 · Cited by 195 · cited 2× · see citing works
“Adult PARG-deficient flies show neurodegeneration, reduced locomotor activity and a short lifespan (77), further highlighting how PAR accumulation is toxic.”
Background
Hsp70 Overexpression Sequesters AIF and Reduces Neonatal Hypoxic/Ischemic Brain Injury
Matsumori, Y., Hong, S. M., Aoyama, K., Fan, Y., Kayama, T., Sheldon, R. A., Vexler, Z. S., Ferriero, D. M., Weinstein, P. R., & Liu, J. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600080 · Cited by 195 · cited 1× · see citing works
“This nuclear apoptosis can be blocked by microinjecting neutralizing antibodies against AIF into the cytosol (32, 49), inhibition of cysteine proteases (62) and overexpression of hsp70 (63, 64).”
Background
Poly(ADP-ribose) polymerase-1 and apoptosis inducing factor in neurotoxicity
Yu, S.-W., Wang, H., Dawson, T. M., & Dawson, V. L. (2003) · Neurobiology of Disease · doi:10.1016/j.nbd.2003.08.008 · Cited by 193 · cited 2× · see citing works
“In neurons for example, different neuronal populations treated with a variety of toxic stimuli exhibit protection and concomitant energy preservation with PARP inhibitors (31, 35).”
Background
Dissociating the dual roles of apoptosis‐inducing factor in maintaining mitochondrial structure and apoptosis
Cheung, E. C., Joza, N. A., Steenaart, N. A. E., McClellan, K. A., Neuspiel, M., McNamara, S., MacLaurin, J. G., Rippstein, P. U., Park, D. S., Shore, G. C., et al. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601276 · Cited by 191 · cited 2× · see citing works
“Translocation of AIF into the nucleus, and not its loss from the mitochondria, kills cells (59).”
Background
Mechanisms of Reduced Striatal NMDA Excitotoxicity in Type I Nitric Oxide Synthase Knock-Out Mice
Ayata, C., Ayata, G., Hara, H., Matthews, R. T., Beal, M. F., Ferrante, R. J., Endres, M., Kim, A. H., Christie, R. H., Waeber, C., et al. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-18-06908.1997 · Cited by 185 · cited 14× · see citing works
“When accumulation of PAR polymer is antagonized by immunodepletion using antiserum to PAR or when PAR polymer is degraded through PARG overexpression, cell death is decreased in both NMDA treated neurons and MNNG treated Hela cells (33, 34).”
BackgroundInfluential
The crystal structure of the mouse apoptosis-inducing factor AIF
Maté, M. J., Ortiz-Lombardı́a, M., Boitel, B., Haouz, A., Tello, D., Susín, S. A., Penninger, J. M., Kroemer, G., & Alzari, P. M. (2002) · Nature Structural Biology · doi:10.1038/nsb793 · Cited by 182 · cited 2× · see citing works
“The structure of the AIF protein reveals an overall positive electrostatic potential and homology to Bph4, a ferredoxin reductase in a dioxygenase from bacteria (52).”
Background
Apoptosis-Inducing Factor Is a Key Factor in Neuronal Cell Death Propagated by BAX-Dependent and BAX-Independent Mechanisms
Cheung, E. C., Melanson-Drapeau, L., Cregan, S. P., Vanderluit, J. L., Ferguson, K. L., McIntosh, W. C., Park, D. S., Bennett, S. A. L., & Slack, R. S. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4261-04.2005 · Cited by 177 · cited 1× · see citing works
“AIF translocation to the nucleus has been observed in different cell types induced to die, including a myriad of cases of neuronal cell death (65), experimental models of Parkinson's disease (66), excitotoxicity (67), perinatal hypoxia-ischemia (68, 69), brain trauma (70), and ischemic stroke (65, 71-73).”
Background
Nuclear Translocation of Apoptosis-Inducing Factor after Focal Cerebral Ischemia
Plesnila, N., Zhu, C., Culmsee, C., Gröger, M., Moskowitz, M. A., & Blomgren, K. (2004) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200404000-00011 · Cited by 168 · cited 1× · see citing works
“AIF translocation to the nucleus has been observed in different cell types induced to die, including a myriad of cases of neuronal cell death (65), experimental models of Parkinson's disease (66), excitotoxicity (67), perinatal hypoxia-ischemia (68, 69), brain trauma (70), and ischemic stroke (65, 71-73).”
Background
Quantitative analysis of the binding affinity of poly(ADP-ribose) to specific binding proteins as a function of chain length
Fahrer, J., Kranaster, R., Altmeyer, M., Marx, A., & Bürkle, A. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm944 · Cited by 159 · cited 2× · see citing works
“PAR binding is selective depending on the PAR chain length and the presence of binding sites on the substrates (1, 81-83).”
Background
Translocation of Apoptosis-Inducing Factor in Vulnerable Neurons after Transient Cerebral Ischemia and in Neuronal Cultures after Oxygen-Glucose Deprivation
Cao, G., Clark, R. S. B., Pei, W., Yin, W., Zhang, F., Sun, F., Graham, S. H., & Chen, J. (2003) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/01.wcb.0000087090.01171.e7 · Cited by 159 · cited 1× · see citing works
“AIF translocation to the nucleus has been observed in different cell types induced to die, including a myriad of cases of neuronal cell death (65), experimental models of Parkinson's disease (66), excitotoxicity (67), perinatal hypoxia-ischemia (68, 69), brain trauma (70), and ischemic stroke (65, 71-73).”
Background
Polymerization of the adenosine 5′-diphosphate-ribose moiety of nicotinamide-adenine dinucleotide by nuclear enzyme. I. Enzymatic reactions
Fujimura, S., Hasegawa, S., Shimizu, Y., & Sügimura, T. (1967) · Biochimica et Biophysica Acta (BBA) - Nucleic Acids and Protein Synthesis · doi:10.1016/0005-2787(67)90043-3 · Cited by 143 · see citing works
Cysteine protease inhibition prevents mitochondrial apoptosis-inducing factor (AIF) release
Yuste, V. J., Moubarak, R. S., Delettre, C., Bras, M., Sancho, P., Robert, N., d’Alayer, J., & Susín, S. A. (2005) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401687 · Cited by 134 · cited 1× · see citing works
“This nuclear apoptosis can be blocked by microinjecting neutralizing antibodies against AIF into the cytosol (32, 49), inhibition of cysteine proteases (62) and overexpression of hsp70 (63, 64).”
Background
Tricarboxylic Acid Cycle Substrates Prevent PARP-Mediated Death of Neurons and Astrocytes
Ying, W., Chen, Y., Alano, C. C., & Swanson, R. A. (2002) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200207000-00002 · Cited by 130 · see citing works
Poly(ADP-Ribose) Polymerase Impairs Early and Long-Term Experimental Stroke Recovery
Goto, S., Xue, R., Sugo, N., Sawada, M., Blizzard, K. K., Poitras, M. F., Johns, D. C., Dawson, T. M., Dawson, V. L., Crain, B. J., et al. (2002) · Stroke · doi:10.1161/01.str.0000014203.65693.1e · Cited by 129 · see citing works
Noncovalent interactions of poly(adenosine diphosphate ribose) with histones
Panzeter, P. L., Realini, C. A., & Althaus, F. R. (1992) · Biochemistry · doi:10.1021/bi00120a014 · Cited by 128 · cited 3× · see citing works
“Non-covalent binding of PAR to proteins is stable, in vitro PAR binding is resistant to strong acids, chaotropes, detergents, and high salt concentrations (80, 81).”
Background
Apoptosis Inducing Factor and PARP‐Mediated Injury in the MPTP Mouse Model of Parkinson's Disease
Wang, H., Shimoji, M., Yu, S.-W., Dawson, T. M., & Dawson, V. L. (2003) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2003.tb07471.x · Cited by 127 · cited 1× · see citing works
“AIF translocation to the nucleus has been observed in different cell types induced to die, including a myriad of cases of neuronal cell death (65), experimental models of Parkinson's disease (66), excitotoxicity (67), perinatal hypoxia-ischemia (68, 69), brain trauma (70), and ischemic stroke (65, 71-73).”
Background
Differences among cell types in NAD+ compartmentalization: A comparison of neurons, astrocytes, and cardiac myocytes
Alano, C. C., Tran, A., Tao, R., Ying, W., Karliner, J. S., & Swanson, R. A. (2007) · Journal of Neuroscience Research · doi:10.1002/jnr.21479 · Cited by 123 · cited 2× · see citing works
“The mitochondrial pool of NAD+ appears to be more relevant for cell death rather than the cytosolic and nuclear pools, as cell death is rescued upon preservation of NAD+ in the mitochondria by cyclosporin A, or replenishment of NAD+ by overepression of the biosynthetic nicotinic acid mononucleotide adenylyltransferase…”
Background
A proteomic approach to the identification of heterogeneous nuclear ribonucleoproteins as a new family of poly(ADP-ribose)-binding proteins
Gagné, J., Hunter, J. M., Labrecque, B., Chabot, B., & Poirier, G. G. (2003) · Biochemical Journal · doi:10.1042/bj20021675 · Cited by 113 · cited 2× · see citing works
“Recent studies indicate that PAR binds to a variety of proteins (1, 83).”
Background
Poly(ADP-ribose) polymerase-1-deficient mice are protected from angiotensin II-induced cardiac hypertrophy
Pillai, J. B., Gupta, M., Rajamohan, S. B., Lang, R. M., Raman, J., & Gupta, M. P. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01124.2005 · Cited by 110 · cited 1× · see citing works
“However, NAD+ replenishment probably prevents cell death through SIRT1 which is unrelated to energy levels (1, 39, 40).”
Background
Studies on the Polymer of Adenosine Diphosphate Ribose
Reeder, R. H., Ueda, K., Honjo, T., Nishizuka, Y., & Hayaishi, O. (1967) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)95948-x · Cited by 104 · cited 2× · see citing works
“Further analysis revealed that poly-ADP ribose, not poly-adenine, is the product of the reaction (8-11).”
Background
Decreases in mouse brain NAD+ and ATP induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): prevention by the poly(ADP-ribose) polymerase inhibitor, benzamide
Cosi, C., & Marien, M. R. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00829-4 · Cited by 87 · cited 6× · see citing works
“Mandir AS, Przedborski S, Jackson-Lewis V, Wang ZQ, Simbulan-Rosenthal CM, Smulson ME, Hoffman BE, Guastella DB, Dawson VL, Dawson TM. Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6- tetrahydropyridine (MPTP)-induced parkinsonism.”
BackgroundInfluential
Nitrosylation precedes caspase‐3 activation and translocation of apoptosis‐inducing factor in neonatal rat cerebral hypoxia‐ischaemia
Zhu, C., Wang, X., Qiu, L., Peeters‐Scholte, C. M. P. C. D., Hagberg, H., & Blomgren, K. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02500.x · Cited by 80 · cited 1× · see citing works
“AIF translocation to the nucleus has been observed in different cell types induced to die, including a myriad of cases of neuronal cell death (65), experimental models of Parkinson's disease (66), excitotoxicity (67), perinatal hypoxia-ischemia (68, 69), brain trauma (70), and ischemic stroke (65, 71-73).”
Background
Poly(ADP-ribose) polymerase inhibition protect neurons and the white matter and regulates the translocation of apoptosis-inducing factor in stroke
Komjáti, K., Mabley, J., Virág, L., Southan, G. J., Salzman, A. L., & Szabó, C. (2004) · International Journal of Molecular Medicine · doi:10.3892/ijmm.13.3.373 · Cited by 71 · cited 1× · see citing works
“AIF translocation to the nucleus has been observed in different cell types induced to die, including a myriad of cases of neuronal cell death (65), experimental models of Parkinson's disease (66), excitotoxicity (67), perinatal hypoxia-ischemia (68, 69), brain trauma (70), and ischemic stroke (65, 71-73).”
Background
Neuroprotective Effects of a Novel Poly(ADP-Ribose) Polymerase-1 Inhibitor, 2-{3-[4-(4-Chlorophenyl)-1-piperazinyl] propyl}-4(3 H)-quinazolinone (FR255595), in an in Vitro Model of Cell Death and in Mouse 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Model of Parkinson’s Disease
Iwashita, A., Yamazaki, S., Mihara, K., Hattori, K., Yamamoto, H., Ishida, J., Matsuoka, N., & Mutoh, S. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.064642 · Cited by 67 · cited 6× · see citing works
“Mandir AS, Przedborski S, Jackson-Lewis V, Wang ZQ, Simbulan-Rosenthal CM, Smulson ME, Hoffman BE, Guastella DB, Dawson VL, Dawson TM. Poly(ADP-ribose) polymerase activation mediates 1-methyl-4-phenyl-1, 2,3,6- tetrahydropyridine (MPTP)-induced parkinsonism.”
BackgroundInfluential
Differential Effect of PARP-2 Deletion on Brain Injury after Focal and Global Cerebral Ischemia
Kofler, J., Otsuka, T., Zhang, Z., Noppens, R. R., Grafe, M. R., Koh, D. W., Dawson, V. L., Murcia, J. M., Hurn, P. D., & Traystman, R. J. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600173 · Cited by 67 · see citing works
Poly(ADP-ribose) Accumulation and Enhancement of Postischemic Brain Damage in 110-kDa Poly(ADP-ribose) Glycohydrolase Null Mice
Cozzi, A., Cipriani, G., Fossati, S., Faraco, G., Formentini, L., Min, W., Cortes, U., Wang, Z., Moroni, F., & Chiarugi, A. (2005) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600222 · Cited by 65 · cited 4× · see citing works
“Similarly in vivo, PAR polymer contributes to neuronal death observed in a mouse model of stroke, since transgenic mice overexpressing PARG subjected to transient MCAO, experience smaller infarcts compared with wild-type mice (33).”
BackgroundInfluential
Effect of Transient Focal Ischemia of Mouse Brain on Energy State and NAD Levels
Paschen, W., Oláh, L., & Mies, G. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0751675.x · Cited by 64 · cited 1× · see citing works
“Paschen et al (43) showed that NAD+ decline does not always correlate with ATP decline in a model of ischemia reperfusion.”
Background
Free radical-mediated neurotoxicity may be caused by inhibition of mitochondrial dehydrogenases in vitro and in vivo
Sheline, C. T., & Wei, L. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2006.02.019 · Cited by 56 · cited 1× · see citing works
“In addition, NAD+ resynthesis requires at least 2-4 molecules of ATP while NAD+ depletion blocks glyceraldehyde 3-dehydrogenase activity leading to the cell investing ATP in glycolysis, but without the return in NAD+ (2, 36, 37).”
Background
Intrinsic Mechanisms of Poly(ADP-Ribose) Neurotoxicity: Three Hypotheses
Chiarugi, A. (2005) · NeuroToxicology · doi:10.1016/j.neuro.2005.01.012 · Cited by 32 · cited 6× · see citing works
“Moreover, PARP-1 KO mice, which are resistant to transient cerebral ischemia-induced damage, exhibit reduced PAR and preserved NAD+ levels (31, 35).”
BackgroundInfluential
Nitric Oxide as a Mediator of Neurotoxicity
Dawson, T. M., Dawson, V. L., & Snyder, S. H. (1993) · PsycEXTRA Dataset · doi:10.1037/e495922006-014 · Cited by 27 · cited 1× · see citing works
“nNOS plays an important role in excitotoxicity since primary brain cultures obtained from nNOS KO mice or wild type cultures treated with NOS inhibitors are resistant to NMDA excitotoxicity (15-19).”
Background
Mechanisms of AIF-Mediated Apoptotic DNA Degradation in Caenorhabditis elegans
Perozo, E., Kloda, A., Cortés, D. M., & Martinac, B. (2002) · Cited by 18 · see citing works

Flagged first, then by citations

Sorted by citations

Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018.
Galluzzi, L., Vitale, I., Aaronson, S. A., Abrams, J. M., Adam, D., Agostinis, P., Alnemri, E. S., Altucci, L., Amelio, I., Andrews, D. W., et al. (2018) · Cell Death & Differentiation · doi:10.1038/s41418-017-0012-4 · Cited by 6,680 · see citing works
The molecular machinery of regulated cell death
Tang, D., Kang, R., Berghe, T. V., Vandenabeele, P., & Kroemer, G. (2019) · Cell Research · doi:10.1038/s41422-019-0164-5 · Cited by 2,591 · see citing works
Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012
Galluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., El-Deiry, W. S., Fulda, S., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2011.96 · Cited by 2,421 · see citing works
“Parthanatos have a role in multiple experimental and physiopathological scenarios, including stroke, diabetes, inflammation and neurodegeneration.(141) In line with the”
Background
PARP inhibition: PARP1 and beyond
Rouleau, M., Patel, A., Hendzel, M. J., Kaufmann, S. H., & Poirier, G. G. (2010) · Nature Reviews Cancer · doi:10.1038/nrc2812 · Cited by 1,298 · see citing works
“( Box 1 ), potentially contributing to a unique form of metabolic cell death, which is now termed parthanato”
Background
Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease
Re, D. P. D., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019) · Physiological Reviews · doi:10.1152/physrev.00022.2018 · Cited by 979 · see citing works
Oxidative stress in the aging substantia nigra and the etiology of Parkinson's disease
Trist, B. G., Hare, D. J., & Double, K. L. (2019) · Aging Cell · doi:10.1111/acel.13031 · Cited by 778 · see citing works
On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1Preprint
Luo, X., & Kraus, W. L. (2012) · Genes & Development · doi:10.1101/gad.183509.111 · Cited by 725 · see citing works
“6; Koh et al. 2005; David et al. 2009).”
BackgroundInfluential
PARPs and ADP-ribosylation: recent advances linking molecular functions to biological outcomes
Gupte, R., Liu, Z., & Kraus, W. L. (2017) · Genes & Development · doi:10.1101/gad.291518.116 · Cited by 681 · see citing works
“These cell death pathways include parthanatos, a unique form of programmed cell death that occurs independently of caspase and is distinct from necrosis and apoptosis (David et al. 2009).”
Background
Parthanatos: mitochondrial‐linked mechanisms and therapeutic opportunities
Fatokun, A. A., Dawson, V. L., & Dawson, T. M. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12416 · Cited by 594 · see citing works
“…leading to externalization of phosphatidylserine, dissipation of the mitochondrial membrane potential, translocation of AIF from the mitochondria to the nucleus, large-scale DNA fragmentation (≈50 kb) and chromatin condensation, followed by cell death (Andrabi et al., 2008; David et al., 2009).”
BackgroundInfluential
Initiation and execution mechanisms of necroptosis: an overview
Grootjans, S., Vanden Berghe, T., & Vandenabeele, P. (2017) · Cell Death & Differentiation · doi:10.1038/cdd.2017.65 · Cited by 566 · see citing works
Oxidative cell death in cancer: mechanisms and therapeutic opportunities
An, X., Yu, W., Liu, J., Tang, D., Li, Y., & Chen, X. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06939-5 · Cited by 568 · see citing works
“Parthanatos is a distinct programmed cell death process driven by the activity of poly(ADP-ribose) polymerase 1 (PARP1) [75].”
Background
Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos)
Wang, Y., Kim, N. S., Haince, J.-F., Kang, H. C., David, K. K., Andrabi, S. A., Poirier, G. G., Dawson, V. L., & Dawson, T. M. (2011) · Science Signaling · doi:10.1126/scisignal.2000902 · Cited by 476 · see citing works
“Excessive activation of PARP-1 leads to an intrinsic cell death program, which has been designated parthanatos (PARP-1–dependent cell death) to distinguish it from necrosis and apoptosis (1, 2).”
BackgroundSelf-citation
Therapeutic applications of PARP inhibitors: Anticancer therapy and beyond
Curtin, N. J., & Szabo, C. (2013) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2013.01.006 · Cited by 369 · see citing works
“…1998; Pieper et al., 1999; Mandir et al., 2000; Ying et al., 2002; Du et al., 2003a; Ying et al., 2005; Hamby et al., 2007; Duan et al., 2007; David et al., 2009) and inhibition of pro-inflammatory mediator production (Ullrich et al., 2001; Koh et al., 2004; Hassa et al., 2006; Kraus, 2008;…”
Background
Regulated necrosis in kidney ischemia-reperfusion injury
Pefanis, A., Ierino, F. L., Murphy, J. M., & Cowan, P. J. (2019) · Kidney International · doi:10.1016/j.kint.2019.02.009 · Cited by 361 · see citing works
Diversity and complexity of cell death: a historical review
Park, W., Wei, S., Kim, B., Kim, B., Bae, S., Chae, Y. C., Ryu, D., & Ha, K. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01078-x · Cited by 364 · see citing works
“It was ﬁ rst discovered by Karen Kate David in 2009 26 .”
Ferroptosis and cell death mechanisms in Parkinson's disease
Guiney, S. J., Adlard, P. A., Bush, A. I., Finkelstein, D. I., & Ayton, S. (2017) · Neurochemistry International · doi:10.1016/j.neuint.2017.01.004 · Cited by 337 · see citing works
“Mice overexpressing A53T mutant αsyn developed αsyn aggregates accompanied by mitochondrial DNA damage, which is a known inducer of apoptosis (Martin et al., 2006).”
Influential
Apoptosis-Inducing Factor: Structure, Function, and Redox Regulation
Sevrioukova, I. F. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3445 · Cited by 338 · see citing works
“Parthanatos is characterized by accumulation of PAR, mitochondrial depolarization, early nuclear translocation of AIF, loss of cellular NAD and ATP, and late caspase activation [reviewed in (5, 50)].”
Background
Emerging mechanisms of lipid peroxidation in regulated cell death and its physiological implications
Zheng, Y., Sun, J., Luo, Z., Li, Y., & Huang, Y. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-07244-x · Cited by 345 · see citing works
“Parthanatos is a poly (ADP-Ribose) polymerase 1 (PARP1)- dependent RCD that is triggered by excessive oxidative stress-induced DNA damage and chromatolysis [130, 131].”
Poly(ADP-ribose) polymerase-dependent energy depletion occurs through inhibition of glycolysis
Andrabi, S. A., Umanah, G. K. E., Chang, C., Stevens, D. A., Karuppagounder, S. S., Gagné, J.-P., Poirier, G. G., Dawson, V. L., & Dawson, T. M. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1405158111 · Cited by 307 · see citing works
“PARP-1 activation plays a prominent role in necrotic cell death; the necrotic cell-death program initiated by PARP-1 activation has been designated “parthanatos” to distinguish it from other forms of cell death (6, 7).”
Background
Mechanisms of melanocyte death in vitiligo
Chen, J., Li, S., & Li, C. (2020) · Medicinal Research Reviews · doi:10.1002/med.21754 · Cited by 312 · see citing works
“Parthanatos is a caspase‐independent RCD activated by oxidative stress‐induced DNA damage.(125) In parthanatos, DNA base injured by oxidative stress triggers poly polymerase‐1 (PARP‐1) hyperactivation.”
Background
Cellular functions of the protein kinase ATM and their relevance to human disease
Lee, J., & Paull, T. T. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00394-2 · Cited by 290 · see citing works
Which cell death modality wins the contest for photodynamic therapy of cancer?
Mishchenko, T. A., Владимировна, Б. И., Gorokhova, A. A., Vedunova, M. V., & Krysko, D. V. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04851-4 · Cited by 278 · see citing works
Aminoacyl-tRNA synthetases as therapeutic targets
Kwon, N. H., Fox, P. L., & Kim, S. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0026-3 · Cited by 271 · see citing works
The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks
Ali, A. A. E., Timinszky, G., Arribas-Bosacoma, R., Kozłowski, M., Hassa, P. O., Hassler, M., Ladurner, A. G., Pearl, L. H., & Oliver, A. W. (2012) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.2335 · Cited by 270 · see citing works
Molecular mechanisms of regulated necrosis
Galluzzi, L., Kepp, O., Krautwald, S., Kroemer, G., & Linkermann, A. (2014) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2014.02.006 · Cited by 258 · see citing works
ROS-induced DNA damage and PARP-1 are required for optimal induction of starvation-induced autophagy
Rodríguez-Vargas, J. M., Ruiz-Magaña, M. J., Ruiz‐Ruiz, C., Majuelos‐Melguizo, J., Peralta-Leal, A., Rodríguez, M. I., Muñoz‐Gámez, J. A., de Almodóvar, M. R., Siles, E., López‐Rivas, A., et al. (2012) · Cell Research · doi:10.1038/cr.2012.70 · Cited by 251 · see citing works
Mitochondrial dysfunction in the development and progression of neurodegenerative diseases
Johnson, J., Mercado‐Ayón, E., Mercado-Ayon, Y., Dong, Y., Halawani, S. M., Ngaba, L. V., & Lynch, D. R. (2020) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2020.108698 · Cited by 246 · see citing works
Crystal Structures of Poly(ADP-ribose) Polymerase-1 (PARP-1) Zinc Fingers Bound to DNA
Langelier, M.-F., Planck, J. L., Roy, S., & Pascal, J. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.202507 · Cited by 239 · see citing works
PARP-1 involvement in neurodegeneration: A focus on Alzheimer’s and Parkinson’s diseases
Martire, S., Mosca, L., & D’Erme, M. (2015) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2015.04.001 · Cited by 228 · see citing works
Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death
Andrabi, S. A., Kang, H. C., Haince, J.-F., Lee, Y.-I., Zhang, J., Chi, Z., West, A. B., Koehler, R. C., Poirier, G. G., Dawson, T. M., et al. (2011) · Nature Medicine · doi:10.1038/nm.2387 · Cited by 216 · see citing works
“This form of cell death has recently been designated parthanatos, to distinguish it from apoptosis, autophagy and necrosi”
Background
Programmed death of macrophages in atherosclerosis: mechanisms and therapeutic targets
Meyer, G. R. Y. D., Zurek, M., Puylaert, P., & Martinet, W. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00957-0 · Cited by 214 · see citing works
“Poly(ADP-ribose) polymerase 1 (PARP1)-dependent cell death (also known as parthanatos) is a form of programmed cell death resulting from poly(ADP-ribose) accumulation and the nuclear translocation of apoptosis-inducing factor 1, mitochondrial (AIFM1) 99 .”
The RING finger protein family in health and disease
Cai, C., Tang, Y., Zhai, J., & Zheng, C. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01152-2 · Cited by 194 · see citing works
“The RNF146, a novel PARsylation-directed ring finger E3 ubiquitin ligase, interacts with Poly(ADP-ribose) (PAR) to inhibit the initiation of Parthanatos, a special form of cell death dependent on PAR in many human diseases, thereby exerting neuroprotective property against glutamate NMDA receptor-mediated excitotoxici…”
Background
Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases
Huang, P., Chen, G., Jin, W., Mao, K., Wan, H., & He, Y. T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23137292 · Cited by 193 · see citing works
“Parthanatos, a kind of new programmed death mode, has been put forward by Professors Ted and Valina Dawson to indicate a caspase-independent cell death subroutine that critically relies on the hyper-activation of poly(ADP-ribose) polymerase 1 (PARP1) [1,2].”
BackgroundInfluential
How neurons die in Alzheimer's disease: Implications for neuroinflammation
Mangalmurti, A., & Lukens, J. R. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2022.102575 · Cited by 186 · see citing works
Beyond DNA repair, the immunological role of PARP ‐1 and its siblings
Rosado, M. M., Bennici, E., Novelli, F., & Pioli, C. (2013) · Immunology · doi:10.1111/imm.12099 · Cited by 178 · see citing works
Cell death pathways of particulate matter toxicity
Peixoto, M. S., Galvão, M. F. D. O., & de Medeiros, S. R. B. (2017) · Chemosphere · doi:10.1016/j.chemosphere.2017.08.076 · Cited by 171 · see citing works
Nicotinamide treatment reduces the levels of oxidative stress, apoptosis, and PARP-1 activity in Aβ(1–42)-induced rat model of Alzheimer's disease
Turunc Bayrakdar, E., Uyanikgil, Y., Kanit, L., Koylu, E., & Yalcin, A. (2014) · Free Radical Research · doi:10.3109/10715762.2013.857018 · Cited by 169 · see citing works
Investigation of PARP-1, PARP-2, and PARG interactomes by affinity-purification mass spectrometry
Isabelle, M., Moreel, X., Gagné, J., Rouleau, M., Ethier, C., Gagné, P., Hendzel, M. J., & Poirier, G. G. (2010) · Proteome Science · doi:10.1186/1477-5956-8-22 · Cited by 164 · see citing works
“The detailed mechanism is yet to be understood, but it has been suggested that pADPr may be shuttled from the nucleus to the cytoplasm via proteins, resulting in AIF translocation, as well as the sequestration of anti-apoptotic proteins or the activation of pro-apoptotic proteins [35,36].”
Background
Multiple cell death modalities and their key features (Review)
Yan, G., Elbadawi, M., & Efferth, T. (2020) · World Academy of Sciences Journal · doi:10.3892/wasj.2020.40 · Cited by 154 · see citing works
“In the nucleus, AIF induces chromatin condensation and DNA breakage (49).”
Background
Research progress on morphology and mechanism of programmed cell death
Chen, Y., Li, X., Yang, M., & Liu, S. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06712-8 · Cited by 160 · see citing works
“It should be noted that in addition to DNA damage, oxidative stress, hypoxia, hypoglycemia, or in ﬂ ammatory signals may also trigger the production of parthanatos [80].”
Background
Neuroprotective Effects of Dexmedetomidine against Glutamate Agonist-induced Neuronal Cell Death Are Related to Increased Astrocyte Brain-derived Neurotrophic Factor Expression
Degos, V., Charpentier, T. L., Chhor, V., Brissaud, O., Lebon, S., Schwendimann, L., Bednareck, N., Passemard, S., Mantz, J., & Gressèns, P. (2013) · Anesthesiology · doi:10.1097/aln.0b013e318286cf36 · Cited by 151 · see citing works
Beyond apoptosis: evidence of other regulated cell death pathways in the ovary throughout development and life
Stringer, J. M., Alesi, L. R., Winship, A., & Hutt, K. J. (2023) · Human Reproduction Update · doi:10.1093/humupd/dmad005 · Cited by 145 · see citing works
“translocation of AIF from mitochondria to the nucleus, resulting in chromatin condensation and nuclear fragmentation (David et al., 2009; Wang et al., 2011).”
Background
Inflammation and Metabolism in Cancer Cell—Mitochondria Key Player
Neagu, M. T., Constantin, C., Popescu, I., Zipeto, D., Tzanakakis, G. N., Nikitovic, D., Fenga, C., Stratakis, C. A., Spandidos, D. A., & Tsatsakis, A. M. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00348 · Cited by 144 · see citing works
ARTD1 (PARP1) activation and NAD+ in DNA repair and cell death
Fouquerel, E., & Sobol, R. W. (2014) · DNA repair · doi:10.1016/j.dnarep.2014.09.004 · Cited by 137 · see citing works
“Dawson and co-workers reported for the first time the toxicity of free pADPr [35].”
Background
Disruption of Poly(ADP-ribosyl)ation Mechanisms Alters Responses of Arabidopsis to Biotic Stress
Adams-Phillips, L. C., Briggs, A. G., & Bent, A. F. (2009) · PLANT PHYSIOLOGY · doi:10.1104/pp.109.148049 · Cited by 136 · see citing works
p53 regulates a non-apoptotic death induced by ROS
Montero, J., Dutta, C., van Bodegom, D., Weinstock, D. M., & Letai, A. G. (2013) · Cell Death and Differentiation · doi:10.1038/cdd.2013.52 · Cited by 134 · see citing works
“polymers (poly(ADP-ribose) seems to have an important role as secondary messenger in parthanatos cell death.(19,23) Inhibition of PARP-1 activity using PARP inhibitors or in KO models confers resistance to necrosis induced by DNA-damaging agents.”
Background
Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications
Sodhi, R. K., Singh, N., & Jaggi, A. S. (2010) · Vascular Pharmacology · doi:10.1016/j.vph.2010.06.003 · Cited by 131 · see citing works
Mechanisms of Regulated Cell Death: Current Perspectives
Santagostino, S. F., Assenmacher, C., Tarrant, J. C., Adedeji, A. O., & Radaelli, E. (2021) · Veterinary Pathology · doi:10.1177/03009858211005537 · Cited by 133 · see citing works
Mechanisms of DNA damage-mediated neurotoxicity in neurodegenerative disease
Welch, G., & Tsai, L. (2022) · The EMBO Reports · doi:10.15252/embr.202154217 · Cited by 129 · see citing works
“Unchecked PARP1 activity can induce cell death by progressive NAD + /ATP depletion and Parthanatos, a cell death signaling pathway triggered by excessive poly(ADP-ribose) (David et al , 2009).”
Cellular mechanisms of hereditary photoreceptor degeneration – Focus on cGMP
Power, M., Das, S., Schütze, K., Marigo, V., Ekström, P. A. R., & Paquet‐Durand, F. (2019) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2019.07.005 · Cited by 121 · see citing works
Phosphoproteomic approach to characterize protein mono- and poly(ADP-ribosyl)ation sites from cells
Daniels, C. M., Ong, S.-E., & Leung, A. K. L. (2014) · Journal of Proteome Research · doi:10.1021/pr401032q · Cited by 119 · see citing works
Mitochondria and reactive oxygen and nitrogen species in neurological disorders and stroke: Therapeutic implications☆
Bolaños, J. P., Moro, M. Á., Lizasoaín, I., & Almeida, Á. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.05.009 · Cited by 119 · see citing works
Inhibitors of PARP: Number crunching and structure gazing
Rudolph, J., Jung, K., & Luger, K. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2121979119 · Cited by 118 · see citing works
“PARP1, the most abundant nuclear protein after histones (11), has many other functions in the nucleus (12), including regulation of replication and transcription via its ability to shape chromatin structure (13), regulation of transcription though direct interactions with transcription factors, and control of cell dea…”
Background
Paraptosis: a unique cell death mode for targeting cancer
Hanson, S., Dharan, A., Jinsha, P. V., Pal, S., Nair, B. G., Kar, R., & Mishra, N. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1159409 · Cited by 117 · see citing works
“The term Parthanatos, is a portmanteau term (parthanatos) derived from “par” (for PAR polymer, synthesized following PARP1 activation), and “Thanatos,” the personification of death in Greek mythology (Andrabi et al., 2008; David et al., 2009; Wang et al., 2009).”
Background
Mitochondria Related Cell Death Modalities and Disease
Tian, C., Liu, Y., Li, Z., Zhu, P., & Zhao, M. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.832356 · Cited by 113 · see citing works
“first proposed the concept of parthanatos in 2009 (David et al., 2009).”
Background
ADP-ribosylhydrolase 3 (ARH3), Not Poly(ADP-ribose) Glycohydrolase (PARG) Isoforms, Is Responsible for Degradation of Mitochondrial Matrix-associated Poly(ADP-ribose)
Niere, M., Mashimo, M., Agledal, L., Dölle, C., Kasamatsu, A., Kato, J., Moss, J., & Ziegler, M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.349183 · Cited by 113 · see citing works
Cell Death Mechanisms of Neurodegeneration
Fan, J., Dawson, T. M., & Dawson, V. L. (2017) · Advances in neurobiology · doi:10.1007/978-3-319-57193-5_16 · Cited by 112 · see citing works
The Role of Excitotoxic Programmed Necrosis in Acute Brain Injury
Fujikawa, D. G. (2015) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2015.03.004 · Cited by 110 · see citing works
“The Dawson laboratory has called their data on MNNG-, H2O2− or NMDA-induced PARP-1 activation, translocation of its substrate poly(ADP-ribose) (PAR),mitochondrial release of full-length or truncated apoptosis-inducing factor (AIF), with its translocation to nuclei, “parthanatos” [71].”
Background
Toxicity of Eosinophil MBP Is Repressed by Intracellular Crystallization and Promoted by Extracellular Aggregation
Soragni, A., Yousefi, S., Stoeckle, C., Soriaga, A. B., Sawaya, M. R., Kozlowski, E., Schmid, I., Radonjic‐Hoesli, S., Boutet, S., Williams, G. J., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.01.026 · Cited by 111 · see citing works
“However, pharmacological inhibition of caspases by addition of (3S)-5-(2,6-difluorophenoxy)-3-[[(2S)-3-methyl-1oxo-2-[(2 quinolinylcarbonyl)amino]butyl]amino]-4-oxo-pentanoic acid hydrate (Q-VD) did not prevent MBP-1-mediated death (Figure 4D; Figure S5C), pointing to the possibility that the cell death observed was a…”
Background
Poly(ADP-ribose) Polymerase-1 in Amyloid Beta Toxicity and Alzheimer's Disease
Strosznajder, J. B., Czapski, G. A., Adamczyk, A., & Strosznajder, R. P. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8258-9 · Cited by 109 · see citing works
“Under massive oxidative stress, PARP-1 overactivation leads to necrotic and apoptotic cell death not only due to energy depletion but also through the action of the PAR polymer and apoptosis-inducing factor (AIF) [18–20].”
Background
Interplay between Cell Death and Cell Proliferation Reveals New Strategies for Cancer Therapy
Loftus, L. V., Amend, S. R., & Pienta, K. J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094723 · Cited by 112 · see citing works
“Cytosolic AIF binds macrophage migratory inhibitory factor (MIF), the primary nuclease instigating parthanatos, and promotes MIF nuclear translocation and subsequent DNA fragmentation [63,65].”
Background
ESCRT-III-mediated membrane repair in cell death and tumor resistance
Liu, J., Kang, R., & Tang, D. (2020) · Cancer Gene Therapy · doi:10.1038/s41417-020-0200-0 · Cited by 107 · see citing works
The role of lysosome in regulated necrosis
Alu, A., Han, X., Ma, X., Wu, M., Wei, Y., & Wei, X. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.07.003 · Cited by 104 · see citing works
PARP1: Structural insights and pharmacological targets for inhibition
Spiegel, J. O., Houten, B. V., & Durrant, J. D. (2021) · DNA repair · doi:10.1016/j.dnarep.2021.103125 · Cited by 104 · see citing works
Different modalities of host cell death and their impact on Mycobacterium tuberculosis infection
Nisa, A., Kipper, F. C., Panigrahy, D., Tiwari, S., Kupz, A., & Subbian, S. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00246.2022 · Cited by 102 · see citing works
Calpain activation is not required for AIF translocation in PARP‐1‐dependent cell death (parthanatos)
Wang, Y., Kim, N. S., Li, X., Greer, P. A., Koehler, R. C., Dawson, V. L., & Dawson, T. M. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06167.x · Cited by 102 · see citing works
Mechanisms of Mitochondrial DNA Repair in Mammals
Zinovkina, L. A. (2018) · Biochemistry (Moscow) · doi:10.1134/s0006297918030045 · Cited by 97 · see citing works
Emerging role of immunogenic cell death in cancer immunotherapy
Arimoto, K., Miyauchi, S., Liu, M., & Zhang, D. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1390263 · Cited by 99 · see citing works
“Poly (ADP-ribose) polymerase-1 (PARP-1), a nuclear protein that plays a crucial role in DNA repair, genomic stability, and transcription is the key molecule in the parthanatos mechanism (112, 113).”
Background
Poly(ADP-ribosyl)ation in regulation of chromatin structure and the DNA damage response
Tallis, M., Morra, R., Barkauskaite, E., & Ahel, I. (2013) · Chromosoma · doi:10.1007/s00412-013-0442-9 · Cited by 94 · see citing works
“Perhaps most significantly, PAR contributes to parthanatos (or PAR-mediated cell death) via an apoptosis-inducing factor (AIF)-mediated mechanism (Barkauskaite et al. 2013; Cregan et al. 2004; David et al. 2009;Wang et al. 2009, 2011).”
Background
The Latest View on the Mechanism of Ferroptosis and Its Research Progress in Spinal Cord Injury
Chen, Y., Liu, S., Li, J., Li, Z., Quan, J., Liu, X., Tang, Y., & Liu, B. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/6375938 · Cited by 97 · see citing works
“apoptosis [5], other nonapoptotic forms of cell death have been discovered in recent years, including necroptosis [6], pyroptosis [7, 8], ferroptosis [9], entosis [10], netosis [11], parthanatos [12], lysosome-dependent cell death [13], autophagy-dependent cell death [14], alkaliptosis [15], and oxeiptosis [16].”
Background
Poly(ADP-ribose) polymerase-1 is a key mediator of cisplatin-induced kidney inflammation and injury
Mukhopadhyay, P., Horváth, B., Kechrid, M., Tanchian, G., Rajesh, M., Naura, A. S., Boulares, A. H., & Pacher, P. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.08.006 · Cited by 94 · see citing works
Immunogenic Cell Death, DAMPs and Prothymosin α as a Putative Anticancer Immune Response Biomarker
Birmpilis, A. I., Paschalis, A., Mourkakis, A., Christodoulou, P., Kostopoulos, I. V., Antimissari, E., Terzoudi, G. I., Georgakilas, A. G., Armpilia, C., Papageorgis, P., et al. (2022) · Cells · doi:10.3390/cells11091415 · Cited by 91 · see citing works
“The key molecule implicated in the mechanism of parthanatos is poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear protein that plays an important role in DNA repair, genomic stability, and transcription [40,41].”
Background
NAMPT inhibition sensitizes pancreatic adenocarcinoma cells to tumor-selective, PAR-independent metabolic catastrophe and cell death induced by β-lapachone
Moore, Z., Chakrabarti, G., Luo, X., Ali, A., Hu, Z., Fattah, F. J., Vemireddy, R., DeBerardinis, R. J., Brekken, R. A., & Boothman, D. A. (2015) · Cell Death and Disease · doi:10.1038/cddis.2014.564 · Cited by 90 · see citing works
Poly(ADP-Ribose)Polymerase (PARP) Inhibitors and Radiation Therapy
Jannetti, S. A., Zeglis, B. M., Zalutsky, M. R., & Reiner, T. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00170 · Cited by 90 · see citing works
“, 2000), parthanatos (David et al., 2009), and mitotic catastrophe (Schoonen and van Vugt, 2018).”
Background
The key players of parthanatos: opportunities for targeting multiple levels in the therapy of parthanatos-based pathogenesis
Liu, L., Li, J., Ke, Y., Zeng, X., Gao, J., Ba, X., & Wang, R. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-04109-w · Cited by 86 · see citing works
The BRCT domain of PARP1 binds intact DNA and mediates intrastrand transfer
Rudolph, J., Muthurajan, U. M., Palacio, M., Mahadevan, J., Roberts, G., Erbse, A. H., Dyer, P. N., & Luger, K. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.11.014 · Cited by 87 · see citing works
Inflammation-induced DNA damage and damage-induced inflammation: a vicious cycle
Palmai‐Pallag, T., & Bachrati, C. Z. (2014) · Microbes and Infection · doi:10.1016/j.micinf.2014.10.001 · Cited by 88 · see citing works
Revisiting the Anti-Cancer Toxicity of Clinically Approved Platinating Derivatives
Forgie, B. N., Prakash, R., & Telleria, C. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315410 · Cited by 86 · see citing works
Viral macrodomains: a structural and evolutionary assessment of the pharmacological potential
Rack, J. G. M., Zorzini, V., Zhu, Z., Schuller, M., Ahel, D., & Ahel, I. (2020) · Open Biology · doi:10.1098/rsob.200237 · Cited by 87 · see citing works
“Similarly, viral PAR-degrading macrodomains could interfere with PARP5-dependent signalling and thus suppress the formation of an antiviral environment (figure 1a).”
Background
PARP inhibitors: New tools to protect from inflammation
Giansanti, V., Donà, F., Tillhon, M., & Scovassi, A. I. (2010) · Biochemical Pharmacology · doi:10.1016/j.bcp.2010.04.022 · Cited by 85 · see citing works
“Notably, PARP-1 is also involved in a paradigm of caspase-independent death called ‘‘parthanatos’’, characterized by the accumulation of poly(ADPribose) and the release of apoptosis inducing factor (AIF) from mitochondria [29,30].”
Background
Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid
Tajuddin, N. F., Moon, K., Marshall, S. A., Nixon, K., Neafsey, E. J., Kim, H., & Collins, M. A. (2014) · PLoS ONE · doi:10.1371/journal.pone.0101223 · Cited by 85 · see citing works
“However, PARP-1 hyperactivation can deplete essential cellular NAD+ levels and ATP, as well as trigger PAR-directed mitochondrial non-apoptotic death, which is termed parthanatos [24].”
Background
How to kill tumor cells with inhibitors of poly(ADP‐ribosyl)ation
Mangerich, A., & Bürkle, A. (2010) · International Journal of Cancer · doi:10.1002/ijc.25683 · Cited by 83 · see citing works
“PARP1 is the founding member of the family of PARPs with pleiotropic function in DNA repair,(6) gene transcription,(16) epigenetic regulation(17) and the regulation of cell death and inflammation.(18) PARP1 accounts for 75–90% of cellular PAR formation upon genotoxic stress, as induced, for instance, by”
Background
Host-Directed Therapies: Modulating Inflammation to Treat Tuberculosis
Krug, S., Parveen, S., & Bishai, W. R. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.660916 · Cited by 84 · see citing works
Necroptosis in cardiovascular disease - a new therapeutic target
Gupta, K., Phan, N., Wang, Q., & Liu, B. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.03.003 · Cited by 84 · see citing works
Metabolic tricks of cancer cells
Hönigová, K., Navrátil, J., Peltanová, B., Polanska, H. H., Raudenská, M., & Masařík, M. (2022) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2022.188705 · Cited by 84 · see citing works
A partnership between the lipid scramblase XK and the lipid transfer protein VPS13A at the plasma membrane
(2022) · doi:10.1073/pnas.2205425119 · Cited by 79 · see citing works
“An additional small folded module is the WWE domain, which is also present in VPS13C (23), the closest human paralog of VPS13A, and in the metazoan orthologs of VPS13A/C. WWE domains in other proteins were shown to bind Poly-ADP-Ribose (PAR) (28, 29).”
BackgroundInfluential
ADP-ribosylation of RNA and DNA: from in vitro characterization to in vivo function
Weixler, L., Schäringer, K., Momoh, J., Lüscher, B., Feijs, K. L. H., & Žaja, R. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkab136 · Cited by 82 · see citing works
“Accumulation of PAR chains in the cytosol has also been described to be accompanied by induction of apoptosis in a process referred to as parthanatos (117,118).”
Background
ROS homeostasis in cell fate, pathophysiology, and therapeutic interventions
Chen, Y.-S., Tian, H., Rong, D., Wang, L., Chen, S., Zeng, J., Xu, H., Mei, J., Wang, L.-Y., Liou, Y., et al. (2025) · Molecular Biomedicine · doi:10.1186/s43556-025-00338-8 · Cited by 87 · see citing works
“…ROS such as •OH directly attack DNA, causing single-strand or double-strand breaks, activating PARP-1, consuming NAD ⁺ and ATP, and generating poly(ADP-ribose), resulting in mitochondrial membrane potential loss and the release of apoptosis-inducing factor, ultimately resulting in cell death [252].”
Quantitative proteomics and dynamic imaging reveal that G3BP-mediated stress granule assembly is poly(ADP-ribose)-dependent following exposure to MNNG-induced DNA alkylation
Isabelle, M., Gagné, J., Gallouzi, I., & Poirier, G. G. (2012) · Journal of Cell Science · doi:10.1242/jcs.106963 · Cited by 82 · see citing works
“Therefore, SGs sheltering of pADPr could prevent AIF release, while preserving and accumulating pADPr in the cytoplasm until cellular mechanisms reaching a critical point in which the cell fate is directed toward pADPr-dependent apoptosis (Andrabi et al., 2008; David et al., 2009).”
Background
AEBP1 is a Novel Oncogene: Mechanisms of Action and Signaling Pathways
Majdalawieh, A. F., Massri, M., & Ro, H.-S. (2020) · Journal of Oncology · doi:10.1155/2020/8097872 · Cited by 78 · see citing works
“(e accumulation of PAR causes nuclear translocation of apoptosisinducing factor (AIF), resulting in DNA fragmentation and eventually cell death [98].”
Background
PARP-1 Modulation of mTOR Signaling in Response to a DNA Alkylating Agent
Éthier, C., Tardif, M., Arul, L., & Poirier, G. G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0047978 · Cited by 78 · see citing works
“several diseases [55], it is important to understand the signaling”
Background
Activation of PARP by Oxidative Stress Induced by β-Amyloid: Implications for Alzheimer’s Disease
Abeti, R., & Duchen, M. R. (2012) · Neurochemical Research · doi:10.1007/s11064-012-0895-x · Cited by 78 · see citing works
“It has been suggested that the cell death that results from PARP-1 overactivation represents a novel type of cell death [16, 38], distinct from apoptosis, caspase-independent apoptosis, necrosis and perhaps autophagy.”
Background
Mechanisms of Pancreatic β-Cell Apoptosis in Diabetes and Its Therapies
Johnson, J. D., & Luciani, D. S. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-90-481-3271-3_19 · Cited by 76 · see citing works
Melatonin and Ischemic Stroke: Mechanistic Roles and Action
Andrabi, S. S., Parvez, S., & Tabassum, H. (2015) · Advances in Pharmacological Sciences · doi:10.1155/2015/384750 · Cited by 77 · see citing works
“Depletion ofNAD causesATPdepletion and drop in cellular energy subsequently leading to cell demise [69].”
Background
AIF-independent parthanatos in the pathogenesis of dry age-related macular degeneration
Jang, K.-H., Do, Y., Son, D., Son, E., Choi, J., & Kim, E. (2017) · Cell Death and Disease · doi:10.1038/cddis.2016.437 · Cited by 77 · see citing works
“30–32 PARP-2 is the closest homolog to PARP-1, displaying 69% similarity in the catalytic domain, and PARP-1 and -2 are responsible for most of the PAR polymer synthesis.33 PARP-1 has multiple cellular roles, acting both in cell survival and in cell death pathways in cell type- and stimulus-dependent manners.34,35 Act…”
Background
USP7 inhibition alters homologous recombination repair and targets CLL cells independently of ATM/p53 functional status.
Agathanggelou, A., Smith, E., Davies, N. J., Kwok, M., Zlatanou, A., Oldreive, C. E., Mao, J., Da Costa, D., Yadollahi, S., Perry, T., et al. (2017) · Blood · doi:10.1182/blood-2016-12-758219 · Cited by 75 · see citing works
“This work was supported grants from Bloodwise, UK, (11045) (T.S.) and Worldwide Cancer Research (13-1012) (G.S.S.).”
Cellular mechanisms of peroxynitrite-induced neuronal death
Ramdial, K., Franco, M. C., & Estévez, Á. G. (2017) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2017.05.008 · Cited by 75 · see citing works
Sphingolipids as Emerging Mediators in Retina Degeneration
Simón, M. V., Spalm, F. H. P., Vera, M. S., & Rotstein, N. P. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00246 · Cited by 73 · see citing works
“Cer induces photoreceptor death in cultured rat retina neurons in a caspase-independent process, involving generation of ROS, increase in mitochondrial permeability, activation of PARP-1 and calpain, accumulation of poly ADP-ribose polymers and nuclear translocation of AIF (Prado Spalm et al., 2018), which are feature…”
BackgroundInfluential
Mitochondrial poly(ADP-ribose) polymerase: The Wizard of Oz at work
Brunyánszki, A., Szczęsny, B., Virág, L., & Szabó, C. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.02.024 · Cited by 73 · see citing works
“A common question, with respect to the PARP-mediated suicide theory (irrespective whether nuclear or mitochondrial PARP is involved) is this: why would evolution not select out such a dangerous, deleterious protein, which catalyzes the demise of the cell? Multiple authors have attempted to address this question in mul…”
Background
(ADP-ribosyl)hydrolases: Structural Basis for Differential Substrate Recognition and Inhibition
Rack, J. G. M., Ariza, A., Drown, B., Henfrey, C., Bartlett, E. J., Shirai, T., Hergenrother, P. J., & Ahel, I. (2018) · Cell chemical biology · doi:10.1016/j.chembiol.2018.11.001 · Cited by 71 · see citing works
“, 2006) has implicated it in PARP1mediated cell death, where it guards against cell death through its ability to degrade PAR chains (David et al., 2009; Mashimo et al., 2013).”
Background

Mitochondrial and Nuclear Cross Talk in Cell Death
Andrabi, S. A., Dawson, T. M., & Dawson, V. L. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.014 · Cited by 378 · see citing works
Poly(ADP-ribose) polymerase-1 and its ambiguous role in cellular life and death
Castedo, M., Lafarge, A., & Kroemer, G. (2023) · Cell Stress · doi:10.15698/cst2023.01.275 · Cited by 9 · see citing works
Poly(ADP-ribose) polymerase: killer or conspirator? The ‘suicide hypothesis’ revisited
Chiarugi, A. (2002) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01902-7 · Cited by 298 · see citing works
PARG activity is required for cell death by parthanatosPreprint
de Moura, R. D., Kopel, B., de Mattos, P. D., Valente, P. F., Santos, A. C., do Nascimento, R. T., Prado, F. M., Medeiros, M. S. D., Setúbal, J. C., de Souza-Pinto, N. C., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.12.724507
Poly (ADP-ribose) (PAR)-dependent cell death in neurodegenerative diseases
Park, H., Kam, T., Dawson, T. M., & Dawson, V. L. (2020) · International review of cytology · doi:10.1016/bs.ircmb.2019.12.009 · Cited by 105 · see citing works

Authors: David, K. K.
Affiliations: Johns Hopkins University (US)
Corresponding author: David, Karen Kate
Venue: Frontiers in Bioscience
Publisher: IMR Press
Published: 2009
Volume: Volume
Issue: 14
Pages: 1116
ISSN: 1093-4715 (ISSN-L)
1093-9946
DOI: 10.2741/3297
PMC: PMC4450718
OpenAlex: W2033004300
Cited by: 450
References: 96
Citations by year: 2026: 25 · 2025: 32 · 2024: 44 · 2023: 35 · 2022: 38 · 2021: 44 · 2020: 30 · 2019: 30 · 2018: 17 · 2017: 23 · 2016: 16 · 2015: 20 · 2014: 20 · 2013: 22 · 2012: 22
FWCI: 1.38
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Frontiers in bioscience (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
National Institute on Aging (R36AG031572)
National Institute of Neurological Disorders and Stroke (P50NS038377)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords: parthanatos, PARP1, poly(ADP-ribose), cell death, DNA repair, stroke, diabetes mellitus, neurodegeneration, inflammation, therapeutic target
MeSH terms: Poly (ADP-Ribose) Polymerase-1, Animals, Humans, Poly(ADP-ribose) Polymerases, Cell Death

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Parthanatos, a messenger of death

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Self-check

Cites

Cited by

Related

Record

About these checks