Document Detail


L-3-hydroxyacyl-CoA dehydrogenase II protects in a model of Parkinson's disease.
MedLine Citation:
PMID:  15236401     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) impairs mitochondrial respiration and damages dopaminergic neurons as seen in Parkinson's disease (PD). Here, we report that L-3-hydroxyacyl-CoA dehydrogenase type II/amyloid binding alcohol dehydrogenase (HADH II/ABAD), a mitochondrial oxidoreductase enzyme involved in neuronal survival, is downregulated in PD patients and in MPTP-intoxicated mice. We also show that transgenic mice with increased expression of human HADH II/ABAD are significantly more resistant to MPTP than their wild-type littermates. This effect appears to be mediated by overexpression of HADH II/ABAD mitigating MPTP-induced impairment of oxidative phosphorylation and ATP production. This study demonstrates that HADH II/ABAD modulates MPTP neurotoxicity and suggests that HADH II/ABAD mimetics may provide protective benefit in the treatment of PD.
Authors:
Kim Tieu; Celine Perier; Miquel Vila; Casper Caspersen; Hui-Ping Zhang; Peter Teismann; Vernice Jackson-Lewis; David M Stern; Shi Du Yan; Serge Przedborski
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Annals of neurology     Volume:  56     ISSN:  0364-5134     ISO Abbreviation:  Ann. Neurol.     Publication Date:  2004 Jul 
Date Detail:
Created Date:  2004-07-05     Completed Date:  2004-08-31     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7707449     Medline TA:  Ann Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  51-60     Citation Subset:  IM    
Affiliation:
Department of Neurology, Columbia University, New York, NY 10032, USA.
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MeSH Terms
Descriptor/Qualifier:
3-Hydroxyacyl CoA Dehydrogenases / genetics,  metabolism*
Animals
Antiparkinson Agents / therapeutic use*
Disease Models, Animal
Dopamine / metabolism
Dopamine Agents / metabolism
Electron Transport / physiology
Female
Humans
Hydrogen Peroxide / metabolism
Isoenzymes / genetics,  metabolism
MPTP Poisoning
Male
Mesencephalon / cytology,  metabolism,  pathology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mitochondria / metabolism*
Neuroprotective Agents / therapeutic use*
Oxidants / metabolism
Oxidative Phosphorylation
Parkinsonian Disorders / chemically induced,  drug therapy*,  metabolism*
Uncoupling Agents / metabolism
Grant Support
ID/Acronym/Agency:
AG021617-01/AG/NIA NIH HHS; AG08702/AG/NIA NIH HHS; AG16223/AG/NIA NIH HHS; AG16736/AG/NIA NIH HHS; AG17490/AG/NIA NIH HHS; NS11766-27A1/NS/NINDS NIH HHS; NS37345/NS/NINDS NIH HHS; NS38370/NS/NINDS NIH HHS; NS38586/NS/NINDS NIH HHS; NS42269/NS/NINDS NIH HHS; NS42855/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
0/Antiparkinson Agents; 0/Dopamine Agents; 0/Isoenzymes; 0/Neuroprotective Agents; 0/Oxidants; 0/Uncoupling Agents; 7722-84-1/Hydrogen Peroxide; EC 1.1.1.35/3-Hydroxyacyl CoA Dehydrogenases

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