Dopamine-derived endogenous N-methyl-(R)-salsolinol: its role in Parkinson's disease.
A dopamine-derived alkaloid, N-methyl-(R)-salsolinol [NM(R)Sal], enantioselectively occurs in human brains and accumulates in the nigrostriatal system. It increases in the cerebrospinal fluid (CSF) of parkinsonian patients and the activity of a neutral (R)-salsolinol [(R)Sal] N-methyltransferase, a key enzyme in the biosynthesis of this toxin, increases in the lymphocytes from parkinsonian patients, suggesting its involvement in the pathogenesis of Parkinson's disease (PD). The studies of animal and cellular models of PD proved that this isoquinoline is selectively cytotoxic to dopamine neurons. Using human dopaminergic SH-SY5Y cells, NM(R)Sal induces apoptosis by the activation of the apoptotic cascade initiated in mitochondria. In this article, we review the recent advance in proving our hypothesis that the dopamine-derived neurotoxin causes the selective depletion of dopamine neurons in PD.
Naoi
Makoto
M
Department of Brain Sciences, Institute of Applied Biochemistry, Yagi Memorial Park, Mitake, 505-0116 Gifu, Japan. mnaoi@giib.or.jp
Maruyama
Wakako
W
Akao
Yukihiro
Y
Yi
Hong
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000503:physiopathology; D012490:Salsoline Alkaloids / Q000134:cerebrospinal fluid / Q000378:metabolism* / Q000633:toxicity; D013237:Stereoisomerism; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D044005:Tetrahydroisoquinolines
D012490:Salsoline Alkaloids; D044005:Tetrahydroisoquinolines; C032837:salsoline; D004298:Dopamine