Selectivity of the parkinsonian neurotoxin MPTP: toxic metabolite MPP+ binds to neuromelanin

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Science  28 Feb 1986:
Vol. 231, Issue 4741, pp. 987-989
DOI: 10.1126/science.3080808


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.

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