Neuromelanin: a role in MPTP-induced neurotoxicity.
Methylphenyltetrahydropyridine (MPTP) selectively destroys melanin-containing neurons in the substantia nigra of humans and other primates. Methylphenylpyridine (MPP+), an active metabolite of MPTP, which is accumulated intraneuronally by the catecholamine uptake system, binds with high affinity to neuromelanin. MPP+ bound intracellularly to neuromelanin may be released gradually, resulting in damage to the neurons of the substantia nigra. Chloroquine, a drug which blocks MPP+ binding to neuromelanin, can protect monkeys from MPTP neurotoxicity.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D002413:Cations, Divalent / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D000882:Haplorhini; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000378:metabolism* / Q000502:physiology*; D011725:Pyridines / Q000633:toxicity*; D011726:Pyridinium Compounds / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002413:Cations, Divalent; D008543:Melanins; D011725:Pyridines; D011726:Pyridinium Compounds; C014121:neuromelanin; D002738:Chloroquine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D015655:1-Methyl-4-phenylpyridinium; D004298:Dopamine; D006719:Homovanillic Acid