Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson's disease

Nature. 1988 Jul 28;334(6180):345-8. doi: 10.1038/334345a0.


In idiopathic Parkinson's disease massive cell death occurs in the dopamine-containing substantia nigra. A link between the vulnerability of nigral neurons and the prominent pigmentation of the substantia nigra, though long suspected, has not been proved. This possibility is supported by evidence that N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its metabolite MPP+, the latter of which causes destruction of nigral neurons, bind to neuromelanin. We have directly tested this hypothesis by a quantitative analysis of neuromelanin-pigmented neurons in control and parkinsonian midbrains. The findings demonstrate first that the dopamine-containing cell groups of the normal human midbrain differ markedly from each other in the percentage of neuromelanin-pigmented neurons they contain. Second, the estimated cell loss in these cell groups in Parkinson's disease is directly correlated (r = 0.97, P = 0.0057) with the percentage of neuromelanin-pigmented neurons normally present in them. Third, within each cell group in the Parkinson's brains, there is greater relative sparing of non-pigmented than of neuromelanin-pigmented neurons. This evidence suggests a selective vulnerability of the neuromelanin-pigmented subpopulation of dopamine-containing mesencephalic neurons in Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • 1-Methyl-4-phenylpyridinium
  • Acetylcholinesterase / analysis
  • Dopamine*
  • Humans
  • Melanins / analysis*
  • Nerve Degeneration*
  • Neurons / analysis*
  • Parkinson Disease / pathology*
  • Pyridines / analysis
  • Pyridinium Compounds / analysis
  • Tyrosine 3-Monooxygenase / analysis


  • Melanins
  • Pyridines
  • Pyridinium Compounds
  • neuromelanin
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Acetylcholinesterase
  • 1-Methyl-4-phenylpyridinium
  • Dopamine