L-dihydroxyphenylalanine and complex I deficiency in Parkinson's disease brain.
There is evidence for a 37% deficiency of complex I activity in Parkinson's disease (PD), which appears to be specific for PD amongst parkinsonian syndromes and selective for the substantia nigra within the central nervous system. Rat studies have shown that, in the context of a normal nigrostriatal dopaminergic cell population, L-dihydroxyphenylalanine (L-dopa) causes a reversible 25% defect of complex I activity in nigral and striatal tissue. Analysis of striatal tissue from PD patients after prolonged exposure to high-dose L-dopa does not show such a defect. Results of these and other studies suggest that L-dopa therapy does not cause complex I deficiency in PD striatum. However, it cannot be excluded that, in the particular environment of the PD substantia nigra, L-dopa may enhance a preexisting complex I defect.
Cooper
J M
JM
Department of Clinical Neurosciences, Royal Free Hospital School of Medicine, London, England, U.K.
Daniel
S E
SE
Marsden
C D
CD
Schapira
A H
AH
D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000172:deficiency*; D009410:Nerve Degeneration / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000473:pathology; D011699:Putamen / Q000187:drug effects / Q000473:pathology; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology
D007980:Levodopa; D016660:NAD(P)H Dehydrogenase (Quinone)