Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin.
Methylphenyltetrahydropyridine (MPTP) selectively destroys neuronal cell bodies in the melanin-containing substantia nigra of humans and other primates. We show that methylphenylpyridine (MPP+), an active metabolite of MPTP which is accumulated intraneuronally by the catecholamine uptake system, binds with high affinity to melanin and neuromelanin. MPP+ bound intracellularly to neuromelanin may be released gradually, resulting in subsequent damage to the neurons of the substantia nigra.
D'Amato
R J
RJ
Lipman
Z P
ZP
Snyder
S H
SH
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D004298:Dopamine / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D008125:Locus Coeruleus / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism* / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000378:metabolism*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D008543:Melanins; D009498:Neurotoxins; D011725:Pyridines; D011726:Pyridinium Compounds; C014121:neuromelanin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine