Nicastrin, Presenilin, APH-1, and PEN-2 Form Active γ-Secretase Complexes in Mitochondria
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Mitochondria are central in the regulation of cell death. Apart from providing the cell with ATP, mitochondria also harbor several death factors that are released upon apoptotic stimuli. Alterations in mitochondrial functions, increased oxidative stress, and neurons dying by apoptosis have been detected in Alzheimer's disease patients. These findings suggest that mitochondria may trigger the abnormal onset of neuronal cell death in Alzheimer's disease. We previously reported that presenilin 1 (PS1), which is often mutated in familial forms of Alzheimer's disease, is located in mitochondria and hypothesized that presenilin mutations may sensitize cells to apoptotic stimuli at the mitochondrial level. Presenilin forms an active gamma-secretase complex together with Nicastrin (NCT), APH-1, and PEN-2, which among other substrates cleaves the beta-amyloid precursor protein (beta-APP) generating the amyloid beta-peptide and the beta-APP intracellular domain. Here we have identified dual targeting sequences (for endoplasmic reticulum and mitochondria) in NCT and showed expression of NCT in mitochondria by immunoelectron microscopy. We also showed that NCT together with APH-1, PEN-2, and PS1 form a high molecular weight complex located in mitochondria. gamma-secretase activity in isolated mitochondria was demonstrated using C83 (alpha-secretase-cleaved C-terminal 83-residue beta-APP fragment from BD8 cells lacking presenilin and thus gamma-secretase activity) or recombinant C100-Flag (C-terminal 100-residue beta-APP fragment) as substrates. Both systems generated an APP intracellular domain, and the activity was inhibited by the gamma-secretase inhibitors l-685,458 or Compound E. This novel localization of NCT, PS1, APH-1, and PEN-2 expands the role and importance of gamma-secretase activity to mitochondria.
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APP and Aβ, as well as the entire γ-secretase complex, physically associate with mitochondria and can effect changes in mitochondrial function.
“accumulating data certainly do suggest APP and Aβ, as well as the entire γ-secretase complex, physically associate with mitochondria and can effect changes in mitochondrial function [58-67].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [65]
Cites
THE MITOCHONDRIAL DEATH/LIFE REGULATOR IN APOPTOSIS AND NECROSIS
Kroemer, G., Dallaporta, B., & Resche-Rigon, M. (1998) · Annual Review of Physiology · doi:10.1146/annurev.physiol.60.1.619 · Cited by 1,971 · see citing works
ABAD Directly Links Aß to Mitochondrial Toxicity in Alzheimer's Disease
Lustbader, J. W., Cirilli, M., Lin, C., Xu, H. W., Takuma, K., Wang, N., Caspersen, C., Chen, X., Pollak, S., Chaney, M., et al. (2004) · Science · doi:10.1126/science.1091230 · Cited by 1,303 · see citing works
Newmeyer, D. D., & Ferguson-Miller, S. M. (2003) · Cell · doi:10.1016/s0092-8674(03)00116-8 · Cited by 1,268 · see citing works
Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing
Yu, G., Nishimura, M., Arawaka, S., Levitan, D. J., Zhang, L., Tandon, A., Song, Y., Rogaeva, E. A., Chen, F., Kawarai, T., et al. (2000) · Nature · doi:10.1038/35024009 · Cited by 906 · see citing works
Reconstitution of γ-secretase activity
Edbauer, D., Winkler, E., Regula, J. T., Pesold, B., Steiner, H., & Haass, C. (2003) · Nature Cell Biology · doi:10.1038/ncb960 · Cited by 882 · see citing works
Photoactivated γ-secretase inhibitors directed to the active site covalently label presenilin 1
Li, Y.-M., Xu, M., Lai, M.-T., Huang, Q., Castro, J. L., DiMuzio-Mower, J., Harrison, T., Lellis, C., Nadin, A., Neduvelil, J. G., et al. (2000) · Nature · doi:10.1038/35015085 · Cited by 866 · see citing works
γ-Secretase is a membrane protein complex comprised of presenilin, nicastrin, aph-1, and pen-2
Kimberly, W. T., LaVoie, M. J., Ostaszewski, B. L., Ye, W., Wolfe, M. S., & Selkoe, D. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1037392100 · Cited by 763 · see citing works
Anandatheerthavarada, H. K., Biswas, G., Robin, M.-A., & Avadhani, N. G. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200207030 · Cited by 571 · see citing works
Brain cytochrome oxidase in Alzheimer's disease
Kish, S. J., Bergeron, C., Rajput, A., Dozic, S., Mastrogiacomo, F., Chang, L., Wilson, J. M., DiStefano, L. M., & Nobrega, J. N. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09439.x · Cited by 537 · see citing works
Presenilin 1 is linked with γ-secretase activity in the detergent solubilized state
Li, Y., Lai, M., Xu, M., Huang, Q., DiMuzio‐Mower, J., Sardana, M. K., Shi, X., Yin, K., Shafer, J. A., & Gardell, S. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.110126897 · Cited by 521 · see citing works
Transition-state analogue inhibitors of γ-secretase bind directly to presenilin-1
Esler, W. P., Kimberly, W. T., Ostaszewski, B. L., Diehl, T. S., Moore, C. L., Tsai, J.-Y., Rahmati, T., Xia, W., Selkoe, D. J., & Wolfe, M. S. (2000) · Nature Cell Biology · doi:10.1038/35017062 · Cited by 514 · see citing works
Electron transport chain defects in Alzheimer's disease brain
Parker, W. D., Parks, J. K., Filley, C. M., & Kleinschmidt-DeMasters, B. K. (1994) · Neurology · doi:10.1212/wnl.44.6.1090 · Cited by 495 · see citing works
Total inactivation of γ–secretase activity in presenilin-deficient embryonic stem cells
Herreman, A., Serneels, L., Annaert, W. G., Collen, D., Schoonjans, L., & Strooper, B. D. (2000) · Nature Cell Biology · doi:10.1038/35017105 · Cited by 481 · see citing works
Suh, Y.-H., & Checler, F. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.3.469 · Cited by 467 · see citing works
Mice lacking both presenilin genes exhibitearlyembryonic patterningdefectsPreprint
Donoviel, D. B., Hadjantonakis, A., Ikeda, M., Zheng, H., George‐Hyslop, P. S., & Bernstein, A. (1999) · Genes & Development · doi:10.1101/gad.13.21.2801 · Cited by 457 · see citing works
Zhang, Y., McLaughlin, R., Goodyer, C., & LeBlanc, A. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200110119 · Cited by 418 · see citing works
Presenilins are required for γ-secretase cleavage of β-APP and transmembrane cleavage of Notch-1
Zhang, Z., Nadeau, P. M., Song, W., Donoviel, D. B., Yuan, M., Bernstein, A., & Yankner, B. A. (2000) · Nature Cell Biology · doi:10.1038/35017108 · Cited by 404 · see citing works
Esler, W. P., Kimberly, W. T., Ostaszewski, B. L., Ye, W., Diehl, T. S., Selkoe, D. J., & Wolfe, M. S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052436599 · Cited by 338 · see citing works
Pasternak, S., Bagshaw, R. D., Guiral, M., Zhang, S., Ackerley, C. A., Pak, B. J., Callahan, J. W., & Mahuran, D. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304009200 · Cited by 314 · see citing works
Steiner, H., Winkler, E., Edbauer, D., Prokop, S., Basset, G., Yamasaki, A., Kostka, M., & Haass, C. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200469200 · Cited by 281 · see citing works
Inhibition of Mitochondrial ATP Generation by Nitric Oxide Switches Apoptosis to Necrosis
Leist, M., Single, B., Naumann, H., Fava, E., Simon, B., Kühnle, S., & Nicotera, P. (1999) · Experimental Cell Research · doi:10.1006/excr.1999.4514 · Cited by 275 · see citing works
The Glutamatergic System and Alzheimer???s Disease
Butterfield, D. A., & Pocernich, C. B. (2003) · CNS Drugs · doi:10.2165/00023210-200317090-00004 · Cited by 267 · see citing works
Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease
Mecocci, P. (2002) · Archives of Neurology · doi:10.1001/archneur.59.5.794 · Cited by 229 · see citing works
Keller, J. N., Guo, Q., Holtsberg, F. W., Bruce‐Keller, A. J., & Mattson, M. P. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-12-04439.1998 · Cited by 214 · see citing works
Lee, S.-F., Shah, S., Li, H., Yu, C., Han, W., & Yu, G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m208164200 · Cited by 210 · see citing works
Wolfe, M. S., Angeles, J. D. L., Miller, D. D., Xia, W., & Selkoe, D. J. (1999) · Biochemistry · doi:10.1021/bi991080q · Cited by 202 · see citing works
Schroeter, E. H., Ilagan, M. X. G., Brunkan, A. L., Hecimovic, S. K., Li, Y., Xu, M., Lewis, H. D., Saxena, M. T., Strooper, B. D., Coonrod, A., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1735338100 · Cited by 197 · see citing works
Herreman, A., Gassen, G. V., Bentahir, M., Nyabi, O., Craessaerts, K., Mueller, U., Annaert, W. G., & Strooper, B. D. (2003) · Journal of Cell Science · doi:10.1242/jcs.00292 · Cited by 195 · see citing works
Presenilin 1 Is Required for Maturation and Cell Surface Accumulation of Nicastrin
Leem, J. Y., Vijayan, S., Han, P., Cai, D., Machura, M., Radomski, K. L., Veselits, M., Xu, H., & Thinakaran, G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c200148200 · Cited by 182 · see citing works
Mature Glycosylation and Trafficking of Nicastrin Modulate Its Binding to Presenilins
Yang, D.-S., Tandon, A., Chen, F., Yu, G., Yu, W. H., Arawaka, S., Hasegawa, H. H., Duthie, M., Schmidt, S. D., Ramabhadran, T. V., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m110871200 · Cited by 157 · see citing works
Partial Purification and Characterization of γ-Secretase from Post-mortem Human Brain
Farmery, M. R., Tjernberg, L. O., Pursglove, S. E., Bergman, A., Winblad, B. G., & Näslund, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211992200 · Cited by 152 · see citing works
Robin, M., Anandatheerthavarada, H. K., Biswas, G., Sepuri, N. B. V., Gordon, D. M., Pain, D., & Avadhani, N. G. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203292200 · Cited by 147 · see citing works
Addya, S., Anandatheerthavarada, H. K., Biswas, G., Bhagwat, S. V., Mullick, J., & Avadhani, N. G. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.139.3.589 · Cited by 137 · see citing works
Anandatheerthavarada, H. K., Biswas, G., Mullick, J., Sepuri, N. B. V., Otvos, L., Pain, D., & Avadhani, N. G. (1999) · The EMBO Journal · doi:10.1093/emboj/18.20.5494 · Cited by 132 · see citing works
Proteomic analysis of human lysosomes: Application to monocytic and breast cancer cells
Journet, A., Chapel, A., Kieffer‐Jaquinod, S., Roux‐Dalvai, F., & Garin, J. (2002) · PROTEOMICS · doi:10.1002/1615-9861(200208)2:8 · Cited by 117 · see citing works
Kimberly, W. T., LaVoie, M. J., Ostaszewski, B. L., Ye, W., Wolfe, M. S., & Selkoe, D. J. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204446200 · Cited by 113 · see citing works
Presenilin-1 is located in rat mitochondria
Ankarcrona, M., & Hultenby, K. R. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00735-0 · Cited by 63 · see citing works
Localization of presenilin–nicastrin complexes and γ‐secretase activity to the trans‐Golgi network
Siman, R., & Velji, J. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01616.x · Cited by 60 · see citing works
Reichmann, H., Fhirke, S., Hebenstreit, G. F., Schrubar, H., & Riederer, P. F. (1993) · Journal of Neurology · doi:10.1007/bf00839971 · Cited by 51 · see citing works
Nicastrin is a resident lysosomal membrane protein
Bagshaw, R. D., Pasternak, S., Mahuran, D. J., & Callahan, J. W. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02865-6 · Cited by 47 · see citing works
Chen, F., Tandon, A., Sanjo, N., Gu, Y., Hasegawa, H., Arawaka, S., Lee, F. J. S., Ruan, X., Mastrangelo, P., Erdebil, S., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m210049200 · Cited by 37 · see citing works
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Mitochondrial Dysfunction and Oxidative Stress in Neurodegenerative Diseases
Lin, M. T., & Beal, M. F. (2006) · Nature · doi:10.1038/nature05292 · Cited by 6,455 · see citing works
Wallace, D. C. (2005) · Annual Review of Genetics · doi:10.1146/annurev.genet.39.110304.095751 · Cited by 3,185 · see citing works
Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942 · see citing works
Manczak, M., Anekonda, T. S., Henson, E., Park, B. S., Quinn, J., & Reddy, P. H. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl066 · Cited by 1,104 · see citing works
Mitochondria in neuroplasticity and neurological disorders
Mattson, M. P., Gleichmann, M., & Cheng, A. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.010 · Cited by 1,081 · see citing works
Mitochondria take center stage in aging and neurodegeneration
Beal, M. F. (2005) · Annals of Neurology · doi:10.1002/ana.20624 · Cited by 957 · see citing works
Mitochondria, oxidative stress and neurodegeneration
Federico, A., Cardaioli, E., Pozzo, P. D., Formichi, P., Gallus, G. N., & Radi, E. (2012) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2012.05.030 · Cited by 790 · see citing works
The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives
Swerdlow, R. H., Burns, J. M., & Khan, S. M. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.09.010 · Cited by 786 · see citing works
Mitochondrial dysfunction is a trigger of Alzheimer's disease pathophysiology
Moreira, P. I., Carvalho, C., Zhu, X., Smith, M. A., & Perry, G. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.10.006 · Cited by 734 · see citing works
Early deficits in synaptic mitochondria in an Alzheimer's disease mouse model
Du, H., Guo, L., Yan, S., Sosunov, A. A., McKhann, G. M., & ShiDu Yan, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006586107 · Cited by 704 · see citing works
Mitochondrial permeability transition in Ca2+-dependent apoptosis and necrosis
Rasola, A., & Bernardi, P. (2011) · Cell Calcium · doi:10.1016/j.ceca.2011.04.007 · Cited by 563 · see citing works
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DiMauro, S., & Schon, E. A. (2008) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094302 · Cited by 536 · see citing works
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Haapasalo, A., & Kovacs, D. M. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-101065 · Cited by 487 · see citing works
Mitochondrial oxidative stress in aging and healthspan
Dai, D., Chiao, Y. A., Marcinek, D. J., Szeto, H. H., & Rabinovitch, P. S. (2014) · Longevity & Healthspan · doi:10.1186/2046-2395-3-6 · Cited by 481 · see citing works
A comprehensive review of signal peptides: Structure, roles, and applications
Owji, H., Nezafat, N., Negahdaripour, M., Hajiebrahimi, A., & Ghasemi, Y. (2018) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2018.06.003 · Cited by 523 · see citing works
McManus, M. J., Murphy, M. P., & Franklin, J. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0552-11.2011 · Cited by 432 · see citing works
Presenilins Are Enriched in Endoplasmic Reticulum Membranes Associated with Mitochondria
Área-Gómez, E., de Groof, A. J. C., Boldogh, I. R., Bird, T. D., Gibson, G. E., Koehler, C. M., Yu, W. H., Duff, K., Yaffe, M. P., Pon, L. A., et al. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.090219 · Cited by 397 · see citing works
Crouch, P. J., Blake, R., Duce, J. A., Ciccotosto, G. D., Li, Q.-X., Barnham, K. J., Curtain, C. C., Cherny, R. A., Cappai, R., Dyrks, T., et al. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4276-04.2005 · Cited by 327 · see citing works
Mitochondria, calcium and cell death: A deadly triad in neurodegeneration
Celsi, F., Pizzo, P., Brini, M., Leo, S., Fotino, C., Pinton, P., & Rizzuto, R. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.02.021 · Cited by 321 · see citing works
γ-Secretase in Alzheimer’s disease
Hur, J. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00754-8 · Cited by 325 · see citing works
A mitochondrial etiology of Alzheimer and Parkinson disease
Coskun, P. E., Wyrembak, J., Schriner, S. E., Chen, H.-W., Marciniack, C., LaFerla, F. M., & Wallace, D. C. (2011) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.08.008 · Cited by 297 · see citing works
Mitochondria: A therapeutic target in neurodegeneration
Moreira, P. I., Zhu, X., Wang, X., Lee, H., Nunomura, A., Petersen, R. B., Perry, G. L., & Smith, M. A. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2009.10.007 · Cited by 286 · see citing works
Umeda, T., Tomiyama, T., Sakama, N., Tanaka, S., Lambert, M. P., Klein, W. L., & Mori, H. (2011) · Journal of Neuroscience Research · doi:10.1002/jnr.22640 · Cited by 264 · see citing works
Mitochondria-associated ER membranes in Alzheimer disease
Schon, E. A., & Area-Gomez, E. (2013) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2012.07.011 · Cited by 261 · see citing works
Esposito, L., Raber, J., Kekonius, L., Yan, F., Yu, G.-Q., Bien-Ly, N., Puoliväli, J., Scearce-Levie, K., Masliah, E., & Mucke, L. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0482-06.2006 · Cited by 254 · see citing works
Mechanisms of Aβ mediated neurodegeneration in Alzheimer's disease
Crouch, P. J., Harding, S.-M. E., White, A. R., Camakaris, J., Bush, A. I., & Masters, C. L. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.07.013 · Cited by 244 · see citing works
Mitochondrial dysfunction in neurodegenerative diseases and cancer
de Moura, M. B., Santana‐Santos, L., & Houten, B. V. (2010) · Environmental and Molecular Mutagenesis · doi:10.1002/em.20575 · Cited by 243 · see citing works
Pathogenesis of Alzheimer's disease.
Swerdlow, R. H. (2007) · PubMed Central · Cited by 236 · see citing works
Role of melatonin in neurodegenerative diseases
Srinivasan, V. J., Pandi-Perumal, S. R., Maestroni, G. J. M., Esquifino, A. I., Hardeland, R., & Cardinali, D. P. (2005) · Neurotoxicity Research · doi:10.1007/bf03033887 · Cited by 232 · see citing works
A key role for MAM in mediating mitochondrial dysfunction in Alzheimer disease
Area-Gomez, E., de Groof, A., Bonilla, E., Montesinos, J., Tanji, K., Boldogh, I., Pon, L., & Schon, E. A. (2018) · Cell Death & Disease · doi:10.1038/s41419-017-0215-0 · Cited by 235 · see citing works
Mitochondrial Medicine for Aging and Neurodegenerative Diseases
Reddy, P. H. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8044-z · Cited by 230 · see citing works
Aleardi, A. M., Benard, G., Augereau, O., Malgat, M., Talbot, J.-C., Mazat, J., Letellier, T., Dachary-Prigent, J., Solaini, G., & Rossignol, R. (2005) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-005-6631-3 · Cited by 225 · see citing works
The Alzheimer's disease mitochondrial cascade hypothesis: an update
Swerdlow, R. H., & Khan, S. M. (2009) · Experimental Neurology · doi:10.1016/j.expneurol.2009.01.011 · Cited by 206 · see citing works
Swerdlow, R. H. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4149 · Cited by 203 · see citing works
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Lezi, E., & Swerdlow, R. H. (2011) · Advances in experimental medicine and biology · doi:10.1007/978-94-007-2869-1_12 · Cited by 204 · see citing works
Degradation of the Amyloid β-Protein by the Novel Mitochondrial Peptidasome, PreP
Falkevall, A., Alikhani, N., Bhushan, S., Pavlov, P. F., Busch, K., Johnson, K. A., Eneqvist, T., Tjernberg, L. O., Ankarcrona, M., & Glaser, E. G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602532200 · Cited by 202 · see citing works
Mitochondrial abnormalities and oxidative imbalance in Alzheimer disease
Zhu, X., Perry, G. L., Moreira, P. I., Aliev, G. M., Cash, A., Hirai, K., & Smith, M. A. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9207 · Cited by 196 · see citing works
Brain mitochondrial dysfunction as a link between Alzheimer's disease and diabetes
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Mitochondria-associated ER membranes and Alzheimer disease
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Kwong, J. Q., Beal, M. F., & Manfredi, G. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03990.x · Cited by 180 · see citing works
Amyloid-β Peptides are Generated in Mitochondria-Associated Endoplasmic Reticulum Membranes
Schreiner, B., Hedskog, L., Wiehager, B., & Ankarcrona, M. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132543 · Cited by 179 · see citing works
Multiple Defects in Energy Metabolism in Alzheimers Disease
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Beel, A. J., Mobley, C. K., Kim, H. J., Tian, F., Hadziselimovic, A., Jap, B. K., Prestegard, J. H., & Sanders, C. R. (2008) · Biochemistry · doi:10.1021/bi800993c · Cited by 173 · see citing works
The mitochondrial permeability transition in neurologic disease
Norenberg, M. D., & RAO, K. (2007) · Neurochemistry International · doi:10.1016/j.neuint.2007.02.008 · Cited by 167 · see citing works
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Raschperger, E., Thyberg, J., Pettersson, S., Philipson, L., Fuxe, J., & Pettersson, R. F. (2006) · Experimental Cell Research · doi:10.1016/j.yexcr.2006.01.025 · Cited by 166 · see citing works
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Prete, D. D., Suski, J., Oulès, B., Debayle, D., Gay, A.-S., Lacas-Gervais, S., Bussiere, R., Bauer, C., Pinton, P., Paterlini-Bréchot, P., et al. (2016) · Journal of Alzheimer's Disease · doi:10.3233/jad-160953 · Cited by 158 · see citing works
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Área-Gómez, E., & Schon, E. A. (2017) · The FASEB Journal · doi:10.1096/fj.201601309 · Cited by 159 · see citing works
Convergence of Amyloid-β and Tau Pathologies on Mitochondria In Vivo
Eckert, A., Schulz, K. L., Rhein, V. F., & Götz, J. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8109-5 · Cited by 158 · see citing works
Leuner, K., Müller, W. E., & Reichert, A. S. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8307-4 · Cited by 157 · see citing works
Huang, M., Chiang, S., Kalinowski, D. S., Bae, D.-H., Sahni, S., & Richardson, D. R. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/6392763 · Cited by 154 · see citing works
Mitochondrial iron homeostasis and its dysfunctions in neurodegenerative disorders
Mena, N. P., Urrutia, P. J., Lourido, F., Carrasco, C. M., & Núñez, M. T. (2015) · Mitochondrion · doi:10.1016/j.mito.2015.02.001 · Cited by 154 · see citing works
Fernández, A., Llacuna, L., Fernández-Checa, J. C., & Colell, A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4909-08.2009 · Cited by 150 · see citing works
The key role of mitochondria in Alzheimer's disease
Moreira, P. I., Cardoso, S. M., Santos, M. S., & Oliveira, C. R. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9202 · Cited by 149 · see citing works
Alzheimer's APP mangles mitochondria
Lin, M. T., & Beal, M. F. (2006) · Nature Medicine · doi:10.1038/nm1106-1241 · Cited by 143 · see citing works
Mitochondria and Neurodegeneration
Petrozzi, L., Ricci, G., Giglioli, N. J., Siciliano, G., & Mancuso, M. (2007) · Bioscience Reports · doi:10.1007/s10540-007-9038-z · Cited by 140 · see citing works
Devi, L., & Ohno, M. (2011) · Neurobiology of Disease · doi:10.1016/j.nbd.2011.09.001 · Cited by 121 · see citing works
Schmidt, C., Lepsverdize, E., L, S., Das, A. M., Pizzo, S. V., Dityatev, A. E., & Schachner, M. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002077 · Cited by 136 · see citing works
Oxidative Damage and Cognitive Dysfunction: Antioxidant Treatments to Promote Healthy Brain Aging
Head, E. (2008) · Neurochemical Research · doi:10.1007/s11064-008-9808-4 · Cited by 137 · see citing works
Amyloid Precursor Protein and Alzheimer’s Disease
Orobets, K. S., & Karamyshev, A. L. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241914794 · Cited by 141 · see citing works
Mitochondrial Ca2+ and neurodegeneration
Calí, T., Ottolini, D., & Brini, M. (2012) · Cell Calcium · doi:10.1016/j.ceca.2012.04.015 · Cited by 128 · see citing works
Mitochondrial Dysfunction—A Pharmacological Target in Alzheimer's Disease
Eckert, G. P., Renner, K., Eckert, S. H., Eckmann, J., Hagl, S., Abdel-Kader, R. M., Kurz, C., Leuner, K., & Muller, W. E. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8271-z · Cited by 126 · see citing works
Mitochondrial dysfunction and Alzheimer's disease
Maruszak, A., & Żekanowski, C. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.07.004 · Cited by 123 · see citing works
Effects of Polyphenols on Brain Ageing and Alzheimer’s Disease: Focus on Mitochondria
Schaffer, S., Asseburg, H., Kuntz, S., Muller, W. E., & Eckert, G. P. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8282-9 · Cited by 123 · see citing works
Alzheimer's disease: diverse aspects of mitochondrial malfunctioning.
Santos, R. X., Correia, S. C., Wang, X., Perry, G. L., Smith, M. A., Moreira, P. I., & Zhu, X. (2010) · Europe PMC (PubMed Central) · Cited by 120 · see citing works
Wakabayashi, T., Craessaerts, K., Bammens, L., Bentahir, M., Borgions, F., Herdewijn, P., Staes, A., Timmerman, E., Vandekerckhove, J., Rubinstein, E., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1978 · Cited by 135 · see citing works
Deconstructing Mitochondrial Dysfunction in Alzheimer Disease
García‐Escudero, V., Martín-Maestro, P., Perry, G. L., & Ávila, J. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/162152 · Cited by 118 · see citing works
Pavlov, P. F., Wiehager, B., Sakai, J., Frykman, S., Behbahani, H., Winblad, B. G., & Ankarcrona, M. (2010) · The FASEB Journal · doi:10.1096/fj.10-157230 · Cited by 113 · see citing works
The Neurodegenerative Mitochondriopathies
Swerdlow, R. H. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1095 · Cited by 112 · see citing works
Mitochondria Dysfunction and Neurodegenerative Disorders: Cause or Consequence
Morais, V. A., & Strooper, B. D. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100345 · Cited by 111 · see citing works
Galea, E., Launay, N., Portero-Otin, M., Ruiz, M., Pamplona, R., Aubourg, P., Ferrer, I., & Pujol, A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2012.02.005 · Cited by 108 · see citing works
Insights into amyloid-β-induced mitochondrial dysfunction in Alzheimer disease
Wang, X., Su, B., Perry, G. L., Smith, M. A., & Zhu, X. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.09.007 · Cited by 102 · see citing works
Glutamatergic alterations and mitochondrial impairment in a murine model of Alzheimer disease
Cassano, T., Serviddio, G., Gaetani, S., Romano, A., Dipasquale, P., Cianci, S., Bellanti, F., Laconca, L., Romano, A. D., Padalino, I., et al. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.09.021 · Cited by 99 · see citing works
Mechanisms of amyloid plaque pathogenesis
Fiala, J. C. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0284-8 · Cited by 98 · see citing works
Amyloid precursor protein and mitochondrial dysfunction in Alzheimer's disease
Anandatheerthavarada, H. K., & Devi, L. (2007) · The Neuroscientist · doi:10.1177/1073858407303536 · Cited by 95 · see citing works
Walls, K. C., Coskun, P. E., Gallegos-Pérez, J.-L., Zadourian, N., Freude, K., Rasool, S., Blurton-Jones, M. M., Green, K. N., & LaFerla, F. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.365890 · Cited by 95 · see citing works
Is Alzheimer's Disease a Disorder of Mitochondria-Associated Membranes?
Schon, E. A., & Área-Gómez, E. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100495 · Cited by 95 · see citing works
Glutamate and Mitochondria: Two Prominent Players in the Oxidative Stress-Induced Neurodegeneration
Cassano, T., Pace, L., Bedse, G., Lavecchia, A. M., Marco, F. D., Gaetani, S., & Serviddio, G. (2015) · Current Alzheimer Research · doi:10.2174/1567205013666151218132725 · Cited by 95 · see citing works
Aging sensitizes toward ROS formation and lipid peroxidation in PS1M146L transgenic mice
Schüssel, K., Frey, C., Jourdan, C., Keil, U., Weber, C. C., Müller-Spahn, F., Müller, W. E., & Eckert, A. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.10.041 · Cited by 94 · see citing works
Ye, X., Tai, W., & Zhang, D. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.11.004 · Cited by 88 · see citing works
Swerdlow, R. H. (2020) · International review of neurobiology · doi:10.1016/bs.irn.2020.01.008 · Cited by 88 · see citing works
Neuronal protein trafficking associated with Alzheimer disease
Tang, B. L. (2009) · Cell Adhesion & Migration · doi:10.4161/cam.3.1.7254 · Cited by 83 · see citing works
Mitochondrial accumulation of APP and Aβ: significance for Alzheimer disease pathogenesis
Pavlov, P. F., Petersen, C. H., Glaser, E. G., & Ankarcrona, M. (2009) · Journal of Cellular and Molecular Medicine · doi:10.1111/j.1582-4934.2009.00892.x · Cited by 82 · see citing works
Abnormal Mitochondrial Dynamics—A Novel Therapeutic Target for Alzheimer's Disease?
Su, B., Wang, X., Bonda, D., Perry, G. L., Smith, M. A., & Zhu, X. (2010) · Molecular Neurobiology · doi:10.1007/s12035-009-8095-7 · Cited by 82 · see citing works
Moreira, P. I. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-111127 · Cited by 81 · see citing works
The Alzheimer’s Disease Mitochondrial Cascade Hypothesis: A Current Overview
Swerdlow, R. H. (2023) · Journal of Alzheimer s Disease · doi:10.3233/jad-221286 · Cited by 83 · see citing works
Alzheimer's Disease and Amyloid: Culprit or Coincidence?
Skaper, S. D. (2012) · International review of neurobiology · doi:10.1016/b978-0-12-386986-9.00011-9 · Cited by 80 · see citing works
Trimmer, P. A., & Borland, M. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.1101 · Cited by 80 · see citing works
Ullah, H., Minno, A. D., Santarcangelo, C., Khan, H. Z., & Daglia, M. (2021) · Antioxidants · doi:10.3390/antiox10040546 · Cited by 81 · see citing works
Mitochondrial biology in Alzheimer’s disease pathogenesis
Galindo, M. F., Ikuta, I., Zhu, X., Casadesús, G., & Jordán, J. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06814.x · Cited by 78 · see citing works
Journal of Parkinson’s disease & Alzheimer’s disease
Gottschalk, W. K., Lutz, M. W., He, Y. T., Saunders, A. M., Burns, D. K., Roses, A. D., & Chiba‐Falek, O. (2014) · Journal of Parkinson’s Disease and Alzheimer’s Disease · doi:10.13188/2376-922x.1000003 · Cited by 78 · see citing works
Aspects of β-Amyloid as a Biomarker for Alzheimer's Disease
Andréasson, U., Portelius, E., Andersson, M. E., Blennow, K., & Zetterberg, H. (2007) · Biomarkers in Medicine · doi:10.2217/17520363.1.1.59 · Cited by 74 · see citing works
Dystrophic neurites of senile plaques in Alzheimer’s disease are deficient in cytochrome c oxidase
Pérez-Gracia, E., Torrejón-Escribano, B., & Ferrer, I. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0370-6 · Cited by 72 · see citing works
Mancuso, M., Orsucci, D., LoGerfo, A., Calsolaro, V., & Siciliano, G. (2010) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-6448-9_4 · Cited by 69 · see citing works
Penna, C. R. R., Perrelli, M.-G., Raimondo, S., Tullio, F., Merlino, A., Moro, F., Geuna, S., Mancardi, D., & Pagliaro, P. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.03.013 · Cited by 68 · see citing works
Stefanova, N. A., Muraleva, N. A., Korbolina, E. E., Владимировна, К. Е., Maksimova, K. Y., & Kolosova, N. G. (2014) · Oncotarget · doi:10.18632/oncotarget.2751 · Cited by 66 · see citing works
The consequences of mitochondrial amyloid β-peptide in Alzheimer's disease
Muirhead, K. E. A., Borger, E., Aitken, L., Conway, S. J., & Gunn‐Moore, F. J. (2010) · Biochemical Journal · doi:10.1042/bj20091941 · Cited by 66 · see citing works
Dror, V., Kalynyak, T. B., Bychkivska, Y., Frey, M. H. Z., Tee, M. C., Jeffrey, K. D., Nguyen, V., Luciani, D. S., & Johnson, J. D. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710601200 · Cited by 64 · see citing works
Mitochondrial Microheteroplasmy and a Theory of Aging and Age-Related Disease
Smigrodzki, R. M., & Khan, S. M. (2005) · Rejuvenation Research · doi:10.1089/rej.2005.8.172 · Cited by 62 · see citing works
- Authors
- Hansson, C. A., Frykman, S., Farmery, M. R., Tjernberg, L. O., Nilsberth, C., Pursglove, S. E., Ito, A., Winblad, B., Cowburn, R. F., Thyberg, J., & Ankarcrona, M.
- Affiliations
- Karolinska Institutet (SE)
- The University of Sydney (AU)
- Corresponding author
- Ankarcrona, Maria
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2004-12
- Volume
- 279
- Issue
- 49
- Pages
- 51654-51660
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2132814291
- Cited by
- 256
- References
- 41
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 8 · 2020: 5 · 2019: 9 · 2018: 8 · 2017: 7 · 2016: 12 · 2015: 7 · 2014: 10 · 2013: 12 · 2012: 22
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- gamma-secretase, mitochondria, nicastrin, presenilin 1, APH-1, Pen-2, Alzheimer's disease, amyloid precursor protein, APP intracellular domain, mitochondrial targeting sequence, neuronal apoptosis, gamma-secretase inhibitors, compound E
- MeSH terms
- Adenosine Triphosphate, Alzheimer Disease, Amino Acid Sequence, Animals, Brain, Cholic Acids, Detergents, Electrophoresis, Polyacrylamide Gel, Endoplasmic Reticulum, Golgi Apparatus, Male, Membrane Glycoproteins, Membrane Proteins, Mitochondria, Molecular Sequence Data, Neurons, Peptide Hydrolases, Endopeptidases, Peptides, Subcellular Fractions, Immunoblotting, Signal Transduction, Amyloid beta-Peptides, Microscopy, Immunoelectron, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Rats, Sprague-Dawley, Apoptosis, Protein Structure, Tertiary, Oxidative Stress, Immunoprecipitation, Rats, Presenilin-1, Amyloid Precursor Protein Secretases
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