beta-Carbolinium cations, endogenous MPP+ analogs, in the lumbar cerebrospinal fluid of patients with Parkinson's disease

Neurology. 1995 Dec;45(12):2240-5. doi: 10.1212/wnl.45.12.2240.

Abstract

We measured beta-carbolinium cations (BC+s) endogenous analogs of the N-methyl-4-phenylpyridinium ion (MPP+), in the lumbar CSF of 22 patients with idiopathic Parkinson's disease (PD) and 11 age-matched controls without any symptoms of parkinsonism. Among the BC+s, 2,9-diemethylnorharmanium cation (2,9-Me2NH+), the most potent neurotoxicant that mirrors MPP+ in mitochondria toxicity, was present in 12 patients with PD but not in controls. Although the 2-monomethylated beta-carbolinium cations (2-MeBC+s), which were present in almost all subjects, registered a slightly higher level in PD patients than in controls, the difference was not significant. The total BC+ content, sum of 2-MeBC+ and 2,9-Me2NH+ levels, was significantly higher in PD patients than in controls. The 2-MeBC+ contents significantly increased with the progression of the PD, but 2,9-Me2NH+ decreased as the disease exacerbated, although levels varied within a wide range. The present results strongly support the hypothesis that "bioactivated" BC+s, especially 2,9-Me2NH+s, may be the endogenous causative factors underlying PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenylpyridinium / cerebrospinal fluid*
  • Aged
  • Aged, 80 and over
  • Carbolines / cerebrospinal fluid*
  • Cations / cerebrospinal fluid*
  • Female
  • Humans
  • Lumbosacral Region
  • Male
  • Middle Aged
  • Parkinson Disease / cerebrospinal fluid*
  • Parkinson Disease / pathology
  • Reference Values

Substances

  • Carbolines
  • Cations
  • 1-Methyl-4-phenylpyridinium