Document Detail


Biochemical mechanism of action of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
MedLine Citation:
PMID:  2672418     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The various biochemical mechanisms considered to explain the selective dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are reviewed. MPTP is metabolized by monoamine oxidase in the brain, ultimately yielding 1-methyl-4-phenylpyridinium cation (MPP+), which is accumulated in dopamine cells by the high-affinity dopamine uptake pump. Cell death appears to reflect a compromise in energy production arising as a result of the Nernstian concentration of MPP+ inside mitochondria and persistent inhibition of Site 1 of the respiratory chain. The structural features underlying each biochemical step involved in the expression of neurotoxicity are described, and the implications of the MPTP phenomenon to efforts aimed at elucidating the pathogenesis of idiopathic parkinsonism are discussed.
Authors:
L M Sayre
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Toxicology letters     Volume:  48     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  1989 Aug 
Date Detail:
Created Date:  1989-10-11     Completed Date:  1989-10-11     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  121-49     Citation Subset:  IM    
Affiliation:
Department of Chemistry, Case Western Reserve University, Cleveland, OH 44106.
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MeSH Terms
Descriptor/Qualifier:
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Animals
Brain / metabolism
Humans
Neurotoxins / metabolism*
Oxidation-Reduction
Parkinson Disease / metabolism*
Pyridines / metabolism*
Chemical
Reg. No./Substance:
0/Neurotoxins; 0/Pyridines; 28289-54-5/1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

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