Document Detail


Neurochemistry and toxin models in Huntington's disease.
MedLine Citation:
PMID:  7866587     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Huntington's disease (HD) is a prototypical neurodegenerative disease characterized by selective loss of neurons in the basal ganglia. Although the gene defect has recently been identified, the mechanism by which it leads to neuronal degeneration remains unknown. We have hypothesized that a defect in oxidative phosphorylation may lead to slow, excitotoxic neuronal degeneration in this illness. Evidence for such a defect is reviewed here, including our recent studies using magnetic resonance imaging spectroscopy that show elevated lactate levels in the basal ganglia and cerebral cortex of patients with HD. If a defect in energy metabolism is responsible for neuronal degeneration in HD, it should be possible to mimic the neurodegenerative process with mitochondrial toxins. Our recent studies with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase, show that it can produce striking similarities to the neuropathologic and neurochemical features of HD in both rodents and primates. If such a mechanism is indeed relevant to the pathogenesis of HD, then agents that can improve oxidative phosphorylation might prove to be efficacious. We found that both coenzyme Q10 and nicotinamide can ameliorate striatal lesions produced by mitochondrial toxins in vivo. Furthermore, they reduced elevated lactate concentrations when administered to patients with HD. This finding raises the possibility that such an approach might prove useful in trying to slow the neurodegenerative process.
Authors:
M F Beal
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Current opinion in neurology     Volume:  7     ISSN:  1350-7540     ISO Abbreviation:  Curr. Opin. Neurol.     Publication Date:  1994 Dec 
Date Detail:
Created Date:  1995-03-27     Completed Date:  1995-03-27     Revised Date:  2013-01-18    
Medline Journal Info:
Nlm Unique ID:  9319162     Medline TA:  Curr Opin Neurol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  542-7     Citation Subset:  IM    
Affiliation:
Massachusetts General Hospital, Boston 02114.
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MeSH Terms
Descriptor/Qualifier:
Animals
Coenzymes
Disease Models, Animal
Energy Metabolism / physiology
Humans
Huntington Disease / drug therapy,  etiology*,  metabolism
Mitochondria / drug effects
Neurotoxins
Niacinamide / therapeutic use
Nitro Compounds
Propionates
Ubiquinone / analogs & derivatives,  therapeutic use
Chemical
Reg. No./Substance:
0/Coenzymes; 0/Neurotoxins; 0/Nitro Compounds; 0/Propionates; 1339-63-5/Ubiquinone; 303-98-0/coenzyme Q10; 504-88-1/3-nitropropionic acid; 98-92-0/Niacinamide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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