A neutral N-methyltransferase activity in the striatum determines the level of an endogenous MPP+-like neurotoxin, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, in the substantia nigra of human brains.
An endogenous MPTP-like dopaminergic neurotoxin, N-methyl(R)salsolinol, increases in the parkinsonian cerebrospinal fluid and accumulates in the human nigro-striatum. An N-methyltransferase specific for (R)salsolinol was found in human brain with optimal pH at 7.0 and 8.5. The correlation of the enzyme activity with the level of N-methyl(R)salsolinol and its oxidation product, 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion was examined in the brain regions. Neutral N-methyltransferase activity in the striatum was found to correlate with the level of the endogenous MPP+-like isoquinolinium ion in the substantia nigra (P < 0.001). Considering that this neutral N-methyltransferase activity increases in parkinsonian lymphocytes, the enzyme may be an endogenous factor in the pathogenesis of Parkinson's disease.
Naoi
M
M
Department of Biosciences, Nagoya Institute of Technology, Japan. naoi@ks.kyy.nitech.ac.jp
Maruyama
W
W
Matsubara
K
K
Hashizume
Y
Y
D002421:Caudate Nucleus / Q000201:enzymology; D003342:Corpus Striatum / Q000201:enzymology*; D005625:Frontal Lobe / Q000201:enzymology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000032:analysis*; D008780:Methyltransferases / Q000378:metabolism*; D011699:Putamen / Q000201:enzymology; D013378:Substantia Nigra / Q000737:chemistry*; D013788:Thalamus / Q000201:enzymology
D007546:Isoquinolines; C089303:N-methylsalsolinium; D008780:Methyltransferases; C118573:salsolinol N-methyltransferase