N-methyl(R)salsolinol and a neutral N-methyltransferase as pathogenic factors in Parkinson's disease.
The pathogenesis of Parkinson's disease is still an enigma. As an endogenous MPTP-like neurotoxin, N-methyl(R)salsolinol was proved to induce parkinsonism in rats and apoptosis in dopaminergic neurons. It is synthesized in the human brain by two enzymes; an (R)salsolinol synthase and an N-methyltransferase, and accumulates in the nigro-striatum in human brains. The activity of a neutral N-methyltransferase in the striatum was found to determine the level of MPP+-like 1,2-dimethyl-6,7-dihydroxyisoquinolinium ion, an oxidation product of N-methyl(R)salsolinol in the substantia nigra. The activity of this N-methyltransferase was found to increase significantly in lymphocytes prepared from parkinsonian patients. In cerebrospinal fluid from untreated parkinsonian patients, N-methyl(R)-salsolinol increases significantly. These results suggest that N-methyl(R)salsolinol and a neutral N-methyltransferase may be endogenous factors in the pathogenesis of Parkinson's disease.
Maruyama
W
W
Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Aichi, Japan.
Strolin-Benedetti
M
M
Naoi
M
M
D000368:Aged; D000704:Analysis of Variance; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000134:cerebrospinal fluid; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008214:Lymphocytes / Q000097:blood / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy / Q000209:etiology; D012490:Salsoline Alkaloids / Q000134:cerebrospinal fluid*; D018709:Statistics, Nonparametric; D044005:Tetrahydroisoquinolines
D000978:Antiparkinson Agents; D012490:Salsoline Alkaloids; D044005:Tetrahydroisoquinolines; D007980:Levodopa; C032837:salsoline; D008780:Methyltransferases; D006719:Homovanillic Acid