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NEUROLOGY 1986;36:250
© 1986 American Academy of Neurology

MPTP

A neurotoxin relevant to the pathophysiology of Parkinson's disease: The 1985 George C. Cotzias Lecture

Solomon H. Snyder and Robert J. D'Amato

Departments of Neuroscience, Pharmacology and Experimental Therapeutics, Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD.

MPTP (N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine) elicits selective destruction of nigrostriatal dopamine neurons in humans and animals along with clinical symptoms of parkinsonism. Recent studies clarify mechanisms accounting for this neurotoxicity. MPTP binds with high affinity to monoamine oxidase, which transforms it to the pyridinium MPP+. MPP+ is selectively concentrated by the dopamine neuronal uptake system. In nigral cells, binding by melanin of MPP+ affords a "depot" release mechanism to maintain prolonged high intracellular concentrations sufficient to destroy cells. PC-12 cells provide a model catecholamine cell culture for screening environmentally occurring substances that may be relevant in the etiology of idiopathic Parkinson's disease.

Address correspondence and reprint requests to Dr. Snyder, Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street. Baltimore, MD 21205.

This essay is derived from the George C. Cotzias lecture of the American Academy of Neurology, Dallas, May 2, 1985.

Supported by USPHS grants MH-18501, DA-00266, RSA award DA-00074 to S.H.S., training grant GM-07309 to R.J.D., and a grant of the Bernard Weinberg Fund.

Accepted for publication November 21, 1985.




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