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Science 28 February 1986:
Vol. 231. no. 4741, pp. 987 - 989
DOI: 10.1126/science.3080808
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Articles

Science, Vol 231, Issue 4741, 987-989
Copyright © 1986 by American Association for the Advancement of Science

articles

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

RJ D'Amato, ZP Lipman, and SH Snyder

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.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals.
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PNAS 105, 17567-17572
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A proposed dual role of neuromelanin in the pathogenesis of Parkinson's disease..
L. Zecca, F. A. Zucca, A. Albertini, E. Rizzio, and R. G. Fariello (2006)
Neurology 67, S8-11
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From the Cover: The surface oxidation potential of human neuromelanin reveals a spherical architecture with a pheomelanin core and a eumelanin surface.
W. D. Bush, J. Garguilo, F. A. Zucca, A. Albertini, L. Zecca, G. S. Edwards, R. J. Nemanich, and J. D. Simon (2006)
PNAS 103, 14785-14789
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The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging.
L. Zecca, A. Stroppolo, A. Gatti, D. Tampellini, M. Toscani, M. Gallorini, G. Giaveri, P. Arosio, P. Santambrogio, R. G. Fariello, et al. (2004)
PNAS 101, 9843-9848
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Substantia nigra neuromelanin: structure, synthesis, and molecular behaviour.
L Zecca, D Tampellini, M Gerlach, P Riederer, R G Fariello, and D Sulzer (2001)
Mol. Pathol. 54, 414-418
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