Effects of an Inhibitor of Poly(ADP-Ribose) Polymerase, Desmethylselegiline, Trientine, and Lipoic Acid in Transgenic ALS Mice

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 eff...

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Bibliographic Details
Published in:	Experimental neurology Vol. 168; no. 2; pp. 419 - 424
Main Authors:	Andreassen, Ole A., Dedeoglu, Alpaslan, Friedlich, Avi, Ferrante, Kimberly L., Hughes, Duncan, Szabo, Cesar, Beal, M.Flint
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier Inc 01-04-2001 Elsevier
Subjects:	Amphetamines - pharmacology Amphetamines - therapeutic use amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - drug therapy Amyotrophic Lateral Sclerosis - genetics Animals apoptosis Biological and medical sciences copper Female free radicals lipoic acid Male Medical sciences Mice Mice, Transgenic Miscellaneous Motor Skills - drug effects Motor Skills - physiology Neuropharmacology Neuroprotective Agents - pharmacology Neuroprotective Agents - therapeutic use oxidative damage Pharmacology. Drug treatments poly(ADP-ribose) polymerase Poly(ADP-ribose) Polymerase Inhibitors Survival Thioctic Acid - pharmacology Thioctic Acid - therapeutic use trienterine Trientine - pharmacology Trientine - therapeutic use Weight Loss - drug effects Weight Loss - physiology free radicals trienterine poly(ADP-ribose) polymerase apoptosis oxidative damage copper lipoic acid amyotrophic lateral sclerosis Translocation Lipoic acid Nervous system diseases Enzyme Trientine Rodentia Amyotrophic lateral sclerosis Superoxide dismutase Neuroprotective agent Survival Vertebrata Chemotherapy Mammalia Treatment Mouse Animal Central nervous system disease Chelating agent Degenerative disease Oxidoreductases Mutation Antidote Copper Spinal cord disease
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-4886 1090-2430
DOI:	10.1006/exnr.2001.7633