II. Neuromelanin: A role in MPTP-induced neurotoxicity

Robert J. D'Amato; Guillermo M. Alexander; Robert J. Schwartzman; Cheryl A. Kitt; Donald L. Price; Solomon H. Snyder

doi:10.1016/0024-3205(87)90297-9

II. Neuromelanin: A role in MPTP-induced neurotoxicity

Robert J. D'Amato, Guillermo M. Alexander, Robert J. Schwartzman, Cheryl A. Kitt, Donald L. Price, Solomon H. Snyder

School of Medicine

Research output: Contribution to journal › Article › peer-review

29 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	705-712
Number of pages	8
Journal	Life Sciences
Volume	40
Issue number	8
DOIs	https://doi.org/10.1016/0024-3205(87)90297-9
State	Published - Feb 23 1987

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)
Pharmacology, Toxicology and Pharmaceutics(all)

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10.1016/0024-3205(87)90297-9

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title = "II. Neuromelanin: A role in MPTP-induced neurotoxicity",

abstract = "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.",

author = "D'Amato, {Robert J.} and Alexander, {Guillermo M.} and Schwartzman, {Robert J.} and Kitt, {Cheryl A.} and Price, {Donald L.} and Snyder, {Solomon H.}",

note = "Funding Information: Supported by USPHS grants MH-18501, NS-16375, AG-03359, AG-05146, NS-20471, RSA award DA-O0074 to SHS, training grant GM-07309 to RJD, the Bernard Weinberg Fund, the Robert L. and Clara G. Patterson trust and the Claster family. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.",

year = "1987",

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doi = "10.1016/0024-3205(87)90297-9",

language = "English (US)",

volume = "40",

pages = "705--712",

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T1 - II. Neuromelanin

T2 - A role in MPTP-induced neurotoxicity

AU - D'Amato, Robert J.

AU - Alexander, Guillermo M.

AU - Schwartzman, Robert J.

AU - Kitt, Cheryl A.

AU - Price, Donald L.

AU - Snyder, Solomon H.

N1 - Funding Information: Supported by USPHS grants MH-18501, NS-16375, AG-03359, AG-05146, NS-20471, RSA award DA-O0074 to SHS, training grant GM-07309 to RJD, the Bernard Weinberg Fund, the Robert L. and Clara G. Patterson trust and the Claster family. Copyright: Copyright 2014 Elsevier B.V., All rights reserved.

PY - 1987/2/23

Y1 - 1987/2/23

N2 - 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.

AB - 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.

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II. Neuromelanin: A role in MPTP-induced neurotoxicity

Abstract

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