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.