Document Detail

Neurochemistry and toxin models in Huntington's disease.
MedLine Citation:
PMID:  7866587     Owner:  NLM     Status:  MEDLINE    
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.
M F Beal
Related Documents :
8509777 - Konzo: a distinct disease entity with selective upper motor neuron damage.
10431767 - Evolution of motor and sensory deficits in amyotrophic lateral sclerosis estimated by n...
11895367 - High molecular weight complexes of mutant superoxide dismutase 1: age-dependent and tis...
11142037 - Striatal tissue transplantation in non-human primates.
2078987 - Results with multichannel topographical bipolar recordings of the visual evoked potenti...
12399547 - Neuroendocrine control of a sexually dimorphic behavior by a few neurons of the pars in...
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    
Massachusetts General Hospital, Boston 02114.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Disease Models, Animal
Energy Metabolism / physiology
Huntington Disease / drug therapy,  etiology*,  metabolism
Mitochondria / drug effects
Niacinamide / therapeutic use
Nitro Compounds
Ubiquinone / analogs & derivatives,  therapeutic use
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

Previous Document:  Metabolic disorders in children.
Next Document:  Metals and free radicals in neurodegeneration.