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Neuromelanin synthesis in rat and human substantia nigra

Journal of Neural Transmission - Parkinson's Disease and Dementia Section volume 2, pages 1–14 (1990)Cite this article

Summary

A relation between neuromelanin synthesis and vulnerability of dopaminergic neurons is suggested by the fact that heavily pigmented cells are preferentially lost in aging and Parkinson's disease and that the dopaminergic neurotoxin MPP+ (1-methyl-4-phenyl-pyridine) binds to neuromelanin. To elucidate the mechanism of neuromelanin synthesis, we studied the formation of melanin in homogenates of human and rat substantia nigra tissue “in vitro”. It was found that enzymatic processes accounted for 70% and 90% of the melanin formation in homogenates of human and rat tissue, respectively. The enzymatic synthesis was due to the activity of monoamine oxidase (MAO), since it was prevented by selective inhibitors of this enzyme. Both MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP+ inhibited melanin formation, probably due to their ability to inhibit MAO. No evidence was found for involvement of cytochrome P-450 monooxigenases, which have been postulated to exist in central catecholaminergic neurons. Proadifen reduced melanin formation, not necessarily because it is an inhibitor of P-450 monooxigenases, but rather as it is also a potent inhibitor of MAO. Some antioxidants like ascorbic acid, but not agents destroying hydrogen peroxide, inhibited melanin formation. The findings suggest that the formation of neuromelanin in the substantia nigra involves MAO and non-enzymatic oxidative processes.

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Author notes

  1. J. M. Rabey

    Present address: Department of Neurology, Tel Aviv Medical Center, 6 Weizmann Street, 64239, Tel Aviv, Israel

Affiliations

  1. Department of Neurology, University of Miami School of Medicine, Miami, Florida, U.S.A.

    J. M. Rabey & F. Hefti

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  1. J. M. Rabey
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  2. F. Hefti
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Rabey, J.M., Hefti, F. Neuromelanin synthesis in rat and human substantia nigra. J Neural Transm Gen Sect 2, 1–14 (1990). https://doi.org/10.1007/BF02251241

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  • DOI: https://doi.org/10.1007/BF02251241

Keywords

  • MPTP
  • MPP+
  • neuromelanin
  • Parkinson's disease