Effects of an Inhibitor of Poly(ADP-Ribose) Polymerase, Desmethylselegiline, Trientine, and Lipoic Acid in Transgenic ALS Mice
Abstract
The development of transgenic mouse models of amyotrophic lateral sclerosis (ALS) allows the testing of neuroprotective agents. We evaluated the effects of five agents in transgenic mice with the G93A Cu,Zn superoxide dismutase mutation. A novel inhibitor of poly(ADP-ribose) polymerase showed no effects on survival. Desmethylselegiline and CGP3466 are agents that exert antiapoptotic effects in vitro by preventing nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase. They had no significant effects on survival in the G93A mice. Trientine, a copper chelator, produced a modest significant increase in survival. Similarly administration of lipoic acid in the diet produced a significant improvement in survival. These results therefore provide evidence for potential therapeutic effects of copper chelators and lipoic acid in the treatment of ALS.
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α-lipoic acid exerts significant neuroprotective effects in transgenic mouse models of HD and ALS.
“We found that α-lipoic acid exerts significant neuroprotective effects in transgenic mouse models of HD and ALS128, 187, 188.”
From Mitochondrial Approaches for Neuroprotection (2008) · cites this paper as [188]
Cites
Rosen, D. R., Siddique, T., Patterson, D., Figlewicz, D. A., Sapp, P., Hentati, A., Donaldson, D., Goto, J., O'Regan, J. P., Deng, H.-X., et al. (1993) · Nature · doi:10.1038/362059a0 · Cited by 7,062 · see citing works
Motor Neuron Degeneration in Mice that Express a Human Cu,Zn Superoxide Dismutase Mutation
Gurney, M. E., Pu, H., Chiu, A. Y., Dal Canto, M. C., Polchow, C. Y., Alexander, D. D., Caliendo, J., Hentati, A., Kwon, Y. W., Deng, H.-X., et al. (1994) · Science · doi:10.1126/science.8209258 · Cited by 4,143 · see citing works
Wong, P. C., Pardo, C. A., Borchelt, D., Lee, M. K., Copeland, N. G., Jenkins, N. A., Sisodia, S. S., Cleveland, D. W., & Price, D. L. (1995) · Neuron · doi:10.1016/0896-6273(95)90259-7 · Cited by 1,439 · see citing works
Bruijn, L. I., Becher, M. W., Lee, M. K., Anderson, K. L., Jenkins, N. A., Copeland, N. G., Sisodia, S. S., Rothstein, J. D., Borchelt, D. R., Price, D. L., et al. (1997) · Neuron · doi:10.1016/s0896-6273(00)80272-x · Cited by 1,341 · see citing works
Aggregation and Motor Neuron Toxicity of an ALS-Linked SOD1 Mutant Independent from Wild-Type SOD1
Bruijn, L. I., Houseweart, M. K., Kato, S., Anderson, K. L., Anderson, S., Ohama, E., Reaume, A. G., Scott, R. W., & Cleveland, D. W. (1998) · Science · doi:10.1126/science.281.5384.1851 · Cited by 1,231 · see citing works
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 · see citing works
Beckman, J. S., Carson, M. A., Smith, C. D. L., & Koppenol, W. H. (1993) · Nature · doi:10.1038/364584a0 · Cited by 876 · see citing works
Altered Reactivity of Superoxide Dismutase in Familial Amyotrophic Lateral Sclerosis
Wiedau‐Pazos, M., Goto, J. J., Rabizadeh, S., Gralla, E. B., Roe, J. A., Lee, M. K., Valentine, J. S., & Bredesen, D. E. (1996) · Science · doi:10.1126/science.271.5248.515 · Cited by 720 · see citing works
Functional Role of Caspase-1 and Caspase-3 in an ALS Transgenic Mouse Model
Li, M., Ona, V. O., Guégan, C., Chen, M., Jackson-Lewis, V. R., Andrews, L. J., Olszewski, A. J., Stieg, P. E., Lee, J.-P., Przedborski, S., et al. (2000) · Science · doi:10.1126/science.288.5464.335 · Cited by 717 · see citing works
Gurney, M. E., Cutting, F. B., Zhai, P., Doble, A., Taylor, C. P., Andrus, P. K., & Hall, E. D. (1996) · Annals of Neurology · doi:10.1002/ana.410390203 · Cited by 647 · see citing works
Estévez, A. G., Crow, J. P., Sampson, J. B., Reiter, C., Zhuang, Y., Richardson, G. J., Tarpey, M. M., Barbeito, L., & Beckman, J. S. (1999) · Science · doi:10.1126/science.286.5449.2498 · Cited by 596 · see citing works
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 · see citing works
Amyotrophic lateral sclerosis: Recent insights from genetics and transgenic mice
Brown, R. H. (1995) · Cell · doi:10.1016/0092-8674(95)90346-1 · Cited by 352 · see citing works
Sawa, A., Khan, A. A., Hester, L. D., & Snyder, S. H. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11669 · Cited by 316 · see citing works
Hagen, T. M., Ingersoll, R. T., Lykkesfeldt, J., Liu, J., Wehr, C. M., Vinarsky, V., Bartholomew, J. C., & Ames, B. N. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.2.411 · Cited by 291 · see citing works
Szabó, C., Virág, L., Cuzzocrea, S., Scott, G. S., Hake, P. W., O’Connor, M., Zingarelli, B., Salzman, A. L., & Kun, E. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.7.3867 · Cited by 262 · see citing works
Kragten, E. A., Lalande, I., Zimmermann, K., Roggo, S. P., Schindler, P. A., Müller, D., van Oostrum, J., Waldmeier, P. C., & Fürst, P. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.10.5821 · Cited by 209 · see citing works
Hydroxyl Radical Formation from Cuprous Ion and Hydrogen Peroxide: A Spin-Trapping Study
Gunther, M. R., Hanna, P. M., Mason, R. P., & Cohen, M. S. (1995) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1995.1068 · Cited by 191 · see citing works
Marangon, K., Devaraj, S., Tirosh, O., Packer, L., & Jialal, I. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00155-0 · Cited by 182 · see citing works
Hottinger, A. F., Fine, E. G., Gurney, M. E., Zurn, A. D., & Aebischer, P. (1997) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1997.tb01511.x · Cited by 181 · see citing works
α-Lipoic acid protects against reperfusion injury following cerebral ischemia in rats
Panigrahi, M., Sadguna, Y., Shivakumar, B. R., Kolluri, S. V. R., Roy, S., Packer, L., & Ravindranath, V. (1996) · Brain Research · doi:10.1016/0006-8993(96)00009-1 · Cited by 176 · see citing works
Carlile, G. W., Chalmers-Redman, R. M. E., Tatton, N. A., Pong, A., Borden, K. L. B., & Tatton, W. G. (2000) · Molecular Pharmacology · doi:10.1016/s0026-895x(24)26436-1 · Cited by 164 · see citing works
Ishitani, R., Tanaka, M., Sunaga, K., Katsube, N. C., & Chuang, D. (1998) · Molecular Pharmacology · doi:10.1124/mol.53.4.701 · Cited by 155 · see citing works
Chen, R., Saunders, P. A., Wei, H., Li, Z., Seth, P. K., & Chuang, D. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09654.1999 · Cited by 122 · see citing works
Wolz, P., & Krieglstein, J. (1996) · Neuropharmacology · doi:10.1016/0028-3908(95)00172-7 · Cited by 95 · see citing works
Lack of apoptosis in mice with ALS
Migheli, A., Atzori, C., Piva, R., Tortarolo, M., Girelli, M., Schiffer, D., & Bendotti, C. (1999) · Nature Medicine · doi:10.1038/12381 · Cited by 93 · see citing works
Age-related changes in LTP and antioxidant defenses are reversed by an α-lipoic acid-enriched diet
McGahon, B., Martin, D. S. D., Horrobin, D. F., & Lynch, M. A. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00050-0 · Cited by 84 · see citing works
Nagano, S., Ogawa, Y., Yanagihara, T., & Sakoda, S. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00227-x · Cited by 81 · see citing works
Whiteman, M., Tritschler, H., & Halliwell, B. B. (1996) · FEBS Letters · doi:10.1016/0014-5793(95)01489-6 · Cited by 81 · see citing works
Mytilineou, C., Leonardi, E. T. K., Radcliffe, P. M., Heinonen, E. H., Han, S.-K., Werner, P., Cohen, G., & Olanow, C. W. (1998) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)37288-x · Cited by 80 · see citing works
Lange, D. J., Murphy, P. L., Diamond, B. E., Appel, V., Lai, E. C., Younger, D. S., & Appel, S. H. (1998) · Archives of Neurology · doi:10.1001/archneur.55.1.93 · Cited by 73 · see citing works
Mytilineou, C., Radcliffe, P. M., & Olanow, C. W. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.68010434.x · Cited by 71 · see citing works
Endres, M., Scott, G. S., Salzman, A. L., Kun, E., Moskowitz, M. A., & Szabó, C. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00381-1 · Cited by 47 · see citing works
Taniguchi, H., Shishido, E., Takeichi, M., & Nose, A. (2000) · Journal of Neurobiology · doi:10.1002/(sici)1097-4695(200001)42:1 · Cited by 35 · see citing works
Scott, G. S., Hake, P. W., Salzman, A. L., & Szabó, C. (1998) · Critical Care Medicine · doi:10.1097/00003246-199801001-00046 · Cited by 6 · see citing works
Flagged first, then by citations
1 of the 36 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Halliwell, B. (2001) · Drugs & Aging · doi:10.2165/00002512-200118090-00004 · Cited by 1,502 · see citing works
From charcot to lou gehrig: deciphering selective motor neuron death in als
Cleveland, D. W., & Rothstein, J. D. (2001) · Nature reviews. Neuroscience · doi:10.1038/35097565 · Cited by 1,389 · see citing works
Transgenics, toxicity and therapeutics in rodent models of mutant SOD1-mediated familial ALS
Turner, B. J., & Talbot, K. (2008) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2008.01.001 · Cited by 495 · see citing works
Mattson, M. P. (2003) · NeuroMolecular Medicine · doi:10.1385/nmm:3:2:65 · Cited by 475 · see citing works
Modification of Brain Aging and Neurodegenerative Disorders by Genes, Diet, and Behavior
Mattson, M. P., Chan, S. L., & Duan, W. (2002) · Physiological Reviews · doi:10.1152/physrev.00004.2002 · Cited by 438 · see citing works
Mitochondrial Diseases of the Brain
Chaturvedi, R. K., & Beal, M. F. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.018 · Cited by 416 · see citing works
“We observed significant neuroprotective effects of α-lipoic acid in transgenic mouse models of HD and ALS[366,430,431].”
BackgroundSelf-citationRole of manganese in neurodegenerative diseases
Bowman, A. B., Kwakye, G. F., Hernández, E. H., & Aschner, M. (2011) · Journal of Trace Elements in Medicine and Biology · doi:10.1016/j.jtemb.2011.08.144 · Cited by 392 · see citing works
“Furthermore, loss of SOD2 activity increases the susceptibility to mitochondrial inhibitor induced toxicity and causes oxidative stress [22].”
BackgroundManganese in Health and Disease
Ávila, D. S., Puntel, R. L., & Aschner, M. (2013) · Metal ions in life sciences · doi:10.1007/978-94-007-7500-8_7 · Cited by 358 · see citing works
Dysregulation of Glutathione Homeostasis in Neurodegenerative Diseases
Johnson, W. M., Wilson‐Delfosse, A. L., & Mieyal, J. J. (2012) · Nutrients · doi:10.3390/nu4101399 · Cited by 354 · see citing works
“compounds (silymarin, curcumin, and alpha lipoic acid) have been reported to display some protection in vivo in various neurodegenerative disease models, including PD (paraquot induced), AD (APPSw mice), ALS (Gly93Ala mice), and HD (R6/2 mice) [184–187].”
BackgroundLost in translation: Treatment trials in the SOD1 mouse and in human ALS
Benatar, M. G. (2007) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.12.015 · Cited by 352 · see citing works
Copper Dyshomeostasis in Neurodegenerative Diseases—Therapeutic Implications
Gromadzka, G., Tarnacka, B., Flaga, A., & Adamczyk, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239259 · Cited by 339 · see citing works
Esposito, E., Rotilio, D., DIMATTEO, V., Giulio, C. D., Cacchio, M., & Algeri, S. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00078-7 · Cited by 327 · see citing works
“Moreover, the copper chelator and thiol compound penicillamine, the copper chelator trientine, carboxyfullerenes, Vitamin E and N-acetylcysteine have been reported to increase the survival time in this mouse model and/or delay the onset of the disease to a small extent [6,7,62,95].”
BackgroundMitochondrial Approaches for Neuroprotection
Chaturvedi, R. K., & Beal, M. F. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1427.027 · Cited by 294 · see citing works
Self-citationAntioxidants as treatment for neurodegenerative disorders
Moosmann, B., & Behl, C. (2002) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.11.10.1407 · Cited by 253 · see citing works
The transition metals copper and iron in neurodegenerative diseases
Rivera-Mancía, S., Pérez‐Neri, I., Rı́os, C., Tristán-López, L. A., Rivera-Espinosa, L., & Montes, S. (2010) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2010.04.010 · Cited by 243 · see citing works
Mitochondria in Amyotrophic Lateral Sclerosis: A Trigger and a Target
Dupuis, L., de Aguilar, J. G., Oudart, H., de Tapia, M., Barbeito, L., & Loeffler, J. (2004) · Neurodegenerative Diseases · doi:10.1159/000085063 · Cited by 150 · see citing works
Manganese toxicity in the central nervous system: the glutamine/glutamate‐γ‐aminobutyric acid cycle
Sidoryk‐Wȩgrzynowicz, M., & Aschner, M. (2013) · Journal of Internal Medicine · doi:10.1111/joim.12040 · Cited by 129 · see citing works
Redox metals homeostasis in multiple sclerosis and amyotrophic lateral sclerosis: a review
Sheykhansari, S., Kozielski, K., Bill, J., Sitti, M., Gemmati, D., Zamboni, P., & Singh, A. V. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-0379-2 · Cited by 120 · see citing works
Copper, Iron, and Manganese Toxicity in Neuropsychiatric Conditions
Tarnacka, B., Jopowicz, A., & Maślińska, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22157820 · Cited by 116 · see citing works
Nuclear poly(ADP-ribose) activity is a therapeutic target in amyotrophic lateral sclerosis
McGurk, L., Mojsilovic‐Petrovic, J., Deerlin, V. M. V., Shorter, J., Kalb, R. G., Lee, V. M., Trojanowski, J. Q., Lee, E. B., & Bonini, N. M. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0586-1 · Cited by 112 · see citing works
“However, pharmacological treatment with a PARP-1 inhibitor had no effect on the lifespan or motor performance of the SOD1 G93A transgenic mouse [6].”
BackgroundNeurodegeneration and Inflammation
DeLegge, M. H., & Smoke, A. (2008) · Nutrition in Clinical Practice · doi:10.1177/011542650802300135 · Cited by 114 · see citing works
Prospects for antiapoptotic drug therapy of neurodegenerative diseases
Waldmeier, P. C. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(03)00025-3 · Cited by 105 · see citing works
Chelation therapy for neurodegenerative diseases
Bolognin, S., Drago, D., Luigi Messori, A., & Zatta, P. F. (2009) · Medicinal Research Reviews · doi:10.1002/med.20148 · Cited by 97 · see citing works
An in vitro screening cascade to identify neuroprotective antioxidants in ALS
Barber, S. C., Higginbottom, A., Mead, R. J., Barber, S., & Shaw, P. J. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.01.019 · Cited by 95 · see citing works
Hilton, J. B. W., Mercer, S. W., Lim, N. K.-H., Faux, N. G., Buncic, G., Beckman, J. S., Roberts, B. R., Donnelly, P. S., White, A. R., & Crouch, P. J. (2017) · Scientific Reports · doi:10.1038/srep42292 · Cited by 94 · see citing works
Copper homeostasis and cuproptosis in health and disease
Yang, Y., Wu, J., Wang, L., Ji, G., & Dang, Y. (2024) · MedComm · doi:10.1002/mco2.724 · Cited by 91 · see citing works
Zhang, X., Chen, S., Li, L., Wang, Q., & Le, W. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.02.020 · Cited by 88 · see citing works
“performance for each mouse was tested three times a week and was repeated three times for each test and the longest time of the rotarod performance was used (Andreassen et al., 2001).”
MethodMcCarty, M. F. (2006) · Medical Hypotheses · doi:10.1016/j.mehy.2006.01.013 · Cited by 87 · see citing works
“Presumably, this explains the versatile neuroprotective activity of lipoic acid in rodents [257–263].”
Tokuda, E., Okawa, E., Watanabe, S., Ono, S.-I., & Marklund, S. L. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.01.001 · Cited by 83 · see citing works
Nagano, S., Fujii, Y., Yamamoto, T., Taniyama, M., Fukada, K., Yanagihara, T., & Sakoda, S. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(02)00014-6 · Cited by 83 · see citing works
Koh, S., Kim, Y., Kim, H. Y., Hwang, S., Lee, C. H., & Kim, S. H. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.03.004 · Cited by 83 · see citing works
Uechi, H., Sridharan, S., Nijssen, J., Bilstein, J., Iglesias‐Artola, J. M., Kishigami, S., Casablancas-Antràs, V., Poser, I., Martinez, E. J., Boczek, E. E., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/721001 · Cited by 82 · see citing works
Copper Homeostasis as a Therapeutic Target in Amyotrophic Lateral Sclerosis with SOD1 Mutations
Tokuda, E., & Furukawa, Y. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17050636 · Cited by 77 · see citing works
“So far, these three copper chelators, D-penicillamine [70], trientine [71,72], and TTM [51,73], have been also tested as potential drugs to normalize the intracellular copper levels and suppress the disease symptoms in hSOD1G93A mice (Table 1).”
BackgroundNicotinamide Adenine Dinucleotide Metabolism and Neurodegeneration
Pehar, M., Harlan, B. A., Killoy, K. M., & Vargas, M. R. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7145 · Cited by 77 · see citing works
“Comparably, one of the earliest developed PARP inhibitors failed to confer protection in an ALS animal model (10).”
Tokuda, E., Ono, S.-I., Ishige, K., Naganuma, A., Ito, Y., & Suzuki, T. (2006) · Toxicology · doi:10.1016/j.tox.2006.09.011 · Cited by 76 · see citing works
Nutrition and Dietary Supplements in Motor Neuron Disease
Rosenfeld, J., & Ellis, A. C. (2008) · Physical Medicine and Rehabilitation Clinics of North America · doi:10.1016/j.pmr.2008.03.001 · Cited by 72 · see citing works
Tokuda, E., Ono, S.-I., Ishige, K., Watanabe, S., Okawa, E., Ito, Y., & Suzuki, T. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.05.011 · Cited by 72 · see citing works
“This putative mechanism might be supported by reports that copper-chelating drugs, such as D-penicillamine and trientine, extended the lifespan of mouse models of ALS (Andreassen et al., 2001; Hottinger et al., 1997; Nagano et al., 2003).”
Harlan, B. A., Killoy, K. M., Pehar, M., Liu, L., Auwerx, J. H., & Vargas, M. R. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113219 · Cited by 70 · see citing works
Song, L., Chen, L., Zhang, X., Li, J., & Le, W. (2014) · BioMed Research International · doi:10.1155/2014/483501 · Cited by 71 · see citing works
“Hematoxylin-eosin (H&E), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) staining were applied to pathologically analyze the skeletal muscles of the ALS mice.”
MethodRetractedTokuda, E., Okawa, E., & Ono, S. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.06310.x · Cited by 68 · see citing works
Reduced creatine kinase activity in transgenic amyotrophic lateral sclerosis mice
Wendt, S., Dedeoglu, A., Speer, O., Wallimann, T., Beal, M. F., & Andreassen, O. A. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00784-0 · Cited by 65 · see citing works
Self-citationSong, L., Gao, Y., Zhang, X., & Le, W. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.05.002 · Cited by 63 · see citing works
Cameron, A., & Rosenfeld, J. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200211000-00005 · Cited by 62 · see citing works
Insights into the mechanisms of copper dyshomeostasis in amyotrophic lateral sclerosis
Gil-Bea, F. J., Aldanondo, G., Lasa-Fernández, H., de Munaín, A. L., & Vallejo‐Illarramendi, A. (2017) · Expert Reviews in Molecular Medicine · doi:10.1017/erm.2017.9 · Cited by 57 · see citing works
Bond, L., Bernhardt, K. D., Madria, P., Sorrentino, K., Scelsi, H. F., & Mitchell, C. S. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00010 · Cited by 57 · see citing works
“…Dadon-Nachum et al., 2011; Shin et al., 2012; Crippa et al., 2013; Wei et al., 2013; Mitchell et al., In vivo All 22 187 Barneoud and Curet, 1999; Andreassen et al., 2001a,b; Ferrante et al., 2001; Kriscenski-Perry et al., 2002; Vleminckx et al., 2002; Klivenyi et al., 2004; Crow et al., 2005;…”
BackgroundInfluentialKim, S. H., Henkel-Tigges, J., Beers, D. R., Şengün, İ. Ş., Simpson, E. P., Goodman, J. C., Engelhardt, J. I., Siklós, L., & Appel, S. H. (2003) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/62.1.88 · Cited by 56 · see citing works
“08) trend toward increased survival of the mSOD1 mouse (4% increase) (79).”
BackgroundPetri, S., Calingasan, N. Y., Alsaied, O. A., Wille, E., Kiaei, M., Friedman, J. E., Baranova, O., Chavez, J. C., & Beal, M. F. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04604.x · Cited by 55 · see citing works
“Administration of the copper chelators penicillamine and trientine has been effective in delaying disease onset, improving motor performance, and extending disease progression in several studies in ALS mouse models (Andreassen et al. 2001; Hottinger et al. 1997; Nagano et al. 2003).”
BackgroundSelf-citationNutritional and exercise-based interventions in the treatment of amyotrophic lateral sclerosis
Patel, B. P., & Hamadeh, M. J. (2009) · Clinical Nutrition · doi:10.1016/j.clnu.2009.06.002 · Cited by 55 · see citing works
Lloret, A., & Beal, M. F. (2019) · Neurochemical Research · doi:10.1007/s11064-019-02809-1 · Cited by 52 · see citing works
Self-citationOxidative Stress Treatment for Clinical Trials in Neurodegenerative Diseases
Ienco, E. C., LoGerfo, A., Carlesi, C., Orsucci, D., Ricci, G., Mancuso, M., & Siciliano, G. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-110164 · Cited by 54 · see citing works
“Some evidences demonstrated that LA exerts significant neuroprotective effects in transgenic mouse models of HD and ALS [69–71].”
Tokuda, E., Okawa, E., Watanabe, S., & Ono, S.-I. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt517 · Cited by 48 · see citing works
Koh, S., Kim, Y., Kim, H. Y., Cho, G. W., Kim, K. S., & Kim, S. H. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05471.x · Cited by 47 · see citing works
“which the ALS model mice could not right themselves within 30 s when placed on their sides on a flat surface, at which time they were killed (Andreassen et al., 2001; Beers et al., 2001; Koh et al., 2006).”
BackgroundMethodInfluentialWang, T., Cheng, J., Wang, S., Wang, X., Jiang, H., Yang, Y., Wang, Y., Zhang, C., Liang, W., & Feng, H. (2018) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2018.05.019 · Cited by 43 · see citing works
Lương, K. V. Q., & Nguyễn, L. (2013) · Molecular Brain · doi:10.1186/1756-6606-6-16 · Cited by 37 · see citing works
“However, treatment of transgenic ALS mice with PARP inhibitors resulted in a non-significant trend toward increased survival [41].”
BackgroundMcCarty, M. F. (2006) · Medical Hypotheses · doi:10.1016/j.mehy.2006.04.067 · Cited by 37 · see citing works
One Universal Common Endpoint in Mouse Models of Amyotrophic Lateral Sclerosis
Solomon, J. A., Tarnopolsky, M. A., & Hamadeh, M. J. (2011) · PLoS ONE · doi:10.1371/journal.pone.0020582 · Cited by 32 · see citing works
Reactive astrocytes express PARP in the central nervous system of SODG93A transgenic mice
Chung, Y. H., Joo, K. M., Lee, Y. J., Shin, D. H., & Ik, C. (2004) · Brain Research · doi:10.1016/j.brainres.2004.01.010 · Cited by 27 · see citing works
Therapies in amyotrophic lateral sclerosis–beyond riluzole
Morrison, K. E. (2002) · Current Opinion in Pharmacology · doi:10.1016/s1471-4892(02)00169-8 · Cited by 26 · see citing works
Fr�lich, L., G�tz, M. E., Weinm�ller, M., Youdim, M. B. H., Barth, N., Dirr, A., Gsell, W., Jellinger, K. A., Beckmann, H., & Riederer, P. F. (2004) · Journal of Neural Transmission · doi:10.1007/s00702-003-0043-5 · Cited by 26 · see citing works
“Moreover, lipoate turned out to be effective in preventing 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity in rats (Aguirre et al., 1999) and improves survival in transgenic mouse models of amyotrophic lateral sclerosis and Huntington’s disease (Andreassen et al., 2001a, b).”
Dib, M. (2003) · Drugs · doi:10.2165/00003495-200363030-00004 · Cited by 24 · see citing works
Therapeutic developments in the treatment of amyotrophic lateral sclerosis
Jackson, M. T., Lladó, J., & Rothstein, J. D. (2002) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.11.10.1343 · Cited by 23 · see citing works
“Administration of lipoic acid in the diet was also found to increase the survival of these mice [125].”
BackgroundEsposito, E., Capasso, M., Tomasso, N. N. D., Corona, C., Pellegrini, F., Uncini, A., Vitaglione, P., Fogliano, V., Piantelli, M., & Sensi, S. L. (2007) · Brain Research · doi:10.1016/j.brainres.2007.06.095 · Cited by 22 · see citing works
Psychotropic and Neurotropic Activity
Vogel, H. G. (2007) · Springer eBooks · doi:10.1007/978-3-540-70995-4_6 · Cited by 20 · see citing works
Copper homeostasis and cuproptosis: implications for neurodegenerative diseases
Tao, F., Lin, M., Meng, X., Huang, L., Zhuo, B., Jiang, S., Deng, S., Meng, Z., & Shi, J. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1688554 · Cited by 18 · see citing works
Nicotinamide Adenine Dinucleotide (NAD + )-Dependent Signaling in Neurological Disorders
Bresque, M., Esteve, D., Pehar, M., & Vargas, M. R. (2023) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0241 · Cited by 12 · see citing works
“However, one of the earliest developed PARP inhibitors failed to confer protection in the hSOD1 G93A ALS mouse model (Andreassen et al., 2001).”
Prevention and Therapy of Neurodegenerative Disorders: Role of Nutritional Antioxidants
Matteo, V. D., Pierucci, M., Giovanni, G. D., & Esposito, E. (2007) · Elsevier eBooks · doi:10.1016/b978-044452809-4/50168-x · Cited by 11 · see citing works
Li, L., Lv, L., Wang, Z., Liu, X., Wang, Q., Zhu, H., Jiang, B., Han, Y., Pan, X., Zhou, X., et al. (2025) · Frontiers in Neurology · doi:10.3389/fneur.2025.1581045 · Cited by 9 · see citing works
Stress-induced nuclear GAPDH: Scientific update and clinical application
Vedula, P., Ishizuka, K., Hayashida, A., Sueo, K., & Sawa, A. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00725 · Cited by 9 · see citing works
“Note that there was a negative report on Omigapil for ALS mouse models [47].”
The Role of Caffeine in Neurodegenerative Diseases
Lương, K. V. Q., & Nguyễn, L. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-411462-3.00028-x · Cited by 5 · see citing works
Animal Models of Neurological Disorders
Deshmukh, R., & Bansal, P. (2017) · Springer eBooks · doi:10.1007/978-981-10-5981-0 · Cited by 5 · see citing works
Copper in Brain and Neurodegeneration
Liddell, J. R., Bush, A. I., & White, A. R. (2004) · Encyclopedia of Inorganic and Bioinorganic Chemistry · doi:10.1002/9781119951438.eibc2143 · Cited by 5 · see citing works
Mechanisms of Excitotoxicity and Excitoprotection
Mattson, M. P. (2004) · Springer eBooks · doi:10.1007/978-1-4419-8959-8_7 · Cited by 4 · see citing works
Aguilera‐Méndez, A., Aguilera-Manuel, K., Saavedra‐Molina, A., Ríos‐Chávez, P., Villafaña, S., Nieto-Aguilar, R., Godínez‐Hernández, D., Ortega-Cuéllar, D., Palomera‐Sánchez, Z., & Gauthereau‐Torres, M. Y. (2026) · Neurology International · doi:10.3390/neurolint18040064 · Cited by 3 · see citing works
Hong, Z., Yi, S., Deng, M., Zhong, Y., Zhao, Y., Li, L., Zhou, H., Xiao, Y., Hu, X., & Niu, L. (2025) · IEEE Transactions on Ultrasonics Ferroelectrics and Frequency Control · doi:10.1109/tuffc.2024.3525143 · Cited by 3 · see citing works
“The onset date of the illness was established using the rotarod test, as per earlier studies [27].”
Turner, M. R., & Leigh, P. N. (2003) · Blue books of practical neurology · doi:10.1016/s1877-3419(09)70122-9 · Cited by 3 · see citing works
Preclinical testing of potential therapeutics for Amyotrophic Lateral Sclerosis
Kaneb, H. (2012) · Spiral (Imperial College London) · doi:10.25560/9606 · Cited by 3 · see citing works
Role of Nutritional Antioxidants in the Prevention and Treatment of Neurodegenerative Disorders
Esposito, E. (2006) · Nutrition and disease prevention · doi:10.1201/9781420019131.ch5 · Cited by 2 · see citing works
Animal Models of Neurological Disorders
Kallman, M. J. (2016) · Springer eBooks · doi:10.1007/978-3-642-27728-3_33-2 · Cited by 2 · see citing works
Role of Poly(ADP-ribose) Polymerase in Brain Inflammation and Neuroinjury
Scott, G. S., Komjáti, K., Besson, V. C., & Szabó, C. (2007) · Springer eBooks · doi:10.1007/978-0-387-30398-7_20 · Cited by 2 · see citing works
ALSUntangled #79: alpha-lipoic acid
Giacobbe, A., Hiana, J. C., Wang, O., Benatar, M. G., Wicks, P. J., Cadavid, J. M., Jhooty, S., McDermott, C. J., Pattee, G. L., Bertorini, T. E., et al. (2025) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2025.2507166 · Cited by 1 · see citing works
“ALA also moderately improved survival time (22).”
Zhang, D., Han, L., Zhang, W., Wang, D., Huo, D., Tan, X., Su, X., Wang, M., Xu, J., Cheng, J., et al. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1681929 · Cited by 1 · see citing works
Potential Therapies for Mitochondrial Dysfunction
Henchcliffe, C., & Beal, M. F. (2011) · Springer eBooks · doi:10.1007/978-0-85729-701-3_13 · Cited by 1 · see citing works
Self-citationChapter 19 Therapies in amyotrophic lateral sclerosis: Options for the near and far future
Lemmens, R., Bosch, L. V. D., & Robberecht, W. (2007) · Handbook of clinical neurology · doi:10.1016/s0072-9752(07)80022-4 · Cited by 1 · see citing works
Animal Models of Neurological Disorders
Kallman, M. J. (2015) · Springer eBooks · doi:10.1007/978-3-319-05392-9_33 · Cited by 1 · see citing works
Advances in Neuroprotection Research for Neurodegenerative Diseases
Götz, M. E., & Riederer, P. F. (2004) · Advances in experimental medicine and biology · doi:10.1007/978-1-4419-8969-7_1 · Cited by 1 · see citing works
Chapter 9 Cellular Biological Effects of Copper/Zinc Superoxide Dismutase Mutations
(2003) · Blue books of practical neurology · doi:10.1016/s1877-3419(09)70110-2
Die Rolle von Mangan bei neurodegenerativen Erkrankungen
Bowman, A. B., Kwakye, G. F., Hernández, E. H., & Aschner, M. (2013) · Perspectives in Medicine · doi:10.1016/j.permed.2011.08.001
Antioxidants and Anti-Inflammatory Drugs in the Treatment of Motor Neuron Disease
Esmaeili, M. A., & Kiaei, M. (2014) · Springer eBooks · doi:10.1007/978-3-642-30018-9_132
Astrocytes release small molecules to protect neurons from oxidative stress
Wang, X. (2009) · cIRcle (University of British Columbia) · doi:10.14288/1.0090451
METALLOTHIONEINS AND NEURODEGENERATIVE DISEASES
Bolognin, S., & Zatta, P. F. (2008) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789812778949_0003
“chelating agents such as D-penicillamine and trientine extend survival in SOD1 transgenic mice (Andreassen et al., 2001; Nagano et al., 2003).”
BackgroundAnimal Models of Neurological Disorders
Kallman, M. J. (2015) · Springer eBooks · doi:10.1007/978-3-642-27728-3_33-1
Nutraceuticals and phytotherapeutics for holistic management of amyotrophic lateral sclerosis
Katiyar, D., Singhal, S., Bansal, P., Nagarajan, K., & Grover, P. (2023) · 3 Biotech · doi:10.1007/s13205-023-03475-5 · Cited by 1 · see citing works
Kokas, M., Ambrus, A., Tretter, L., & Komlódi, T. (2026) · Biochemistry (Moscow) · doi:10.1134/s0006297926600663
“Beal’s group previously reported that lipoic acid may exert beneficial effects in neurodegenerative disorders, including Huntington’s disease and amyotrophic lateral sclerosis (ALS) [109-111].”
Copper Homeostasis and Cuproptosis in Neurodegenerative Diseases
Liu, B., Zhang, L., Lv, B., Xu, C., Han, L., Yan, Q., & Wang, X. (2026) · Cells · doi:10.3390/cells15141238
“Furthermore, the copper chelators D-penicillamine and trientine have also been shown to extend the survival time of ALS mouse models [154,155].”
Milardi, D., Han, J., Lee, H. J., Ding, F., Miller, Y., Faller, P., Bush, A. I., Crouch, P. J., Finkelstein, D. I., Double, K. L., et al. (2026) · Chemical Reviews · doi:10.1021/acs.chemrev.5c00420
Gong, Z., & Wei, B. (2026) · Journal of Genetic Engineering and Biotechnology · doi:10.1016/j.jgeb.2026.100835
“9,10 Conversely, the administration of Cu 2 + chelating agents, such as D-penicillamine, 11 trien-tine, 12,13 and ammonia tetrathiomolybdate (TTM), 14 effectively improves clinical symptoms and prolongs the median survival time by reducing Cu 2 + levels.”
- Authors
- Andreassen, O. A., Dedeoglu, A., Friedlich, A., Ferrante, K. L., Hughes, D., Szabo, C., & Beal, M. F.
- Affiliations
- Harvard University (US)
- NewYork–Presbyterian Hospital (US)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2001-04
- Volume
- 168
- Issue
- 2
- Pages
- 419-424
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2057312726
- Cited by
- 96
- References
- 36
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 1 · 2023: 2 · 2021: 1 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 3 · 2013: 8 · 2012: 2
- FWCI
- 5.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Defense
- ALS Association
- National Institute on Aging (P01-AG12292)
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- amyotrophic lateral sclerosis, PARP inhibitors, triethylenetetramine, copper chelation, alpha-lipoic acid, neuroprotection, survival, apoptosis
- MeSH terms
- Poly(ADP-ribose) Polymerase Inhibitors, Amphetamines, Amyotrophic Lateral Sclerosis, Animals, Female, Thioctic Acid, Male, Mice, Transgenic, Motor Skills, Survival, Trientine, Weight Loss, Neuroprotective Agents, Mice
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