beta-Carbolinium cations, endogenous MPP+ analogs, in the lumbar cerebrospinal fluid of patients with Parkinson's disease.
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.
Matsubara
K
K
Department of Legal Medicine, Shimane Medical University, Izumo, Japan.
Kobayashi
S
S
Kobayashi
Y
Y
Yamashita
K
K
Koide
H
H
Hatta
M
M
Iwamoto
K
K
Tanaka
O
O
Kimura
K
K
D015655:1-Methyl-4-phenylpyridinium / Q000134:cerebrospinal fluid*; D000368:Aged; D000369:Aged, 80 and over; D002243:Carbolines / Q000134:cerebrospinal fluid*; D002412:Cations / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008161:Lumbosacral Region; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000473:pathology; D012016:Reference Values
D002243:Carbolines; D002412:Cations; D015655:1-Methyl-4-phenylpyridinium