Cell death in Parkinson's disease.
The cause of neuronal cell death in Parkinson's disease is still an enigma. However, recent results obtained by analyses of postmortem brain suggest that a mitochondria-dependent apoptotic signal was activated. The involvement of dopamine-derived endogenous neurotoxin in the pathogenesis of PD was also indicated. N-Methyl( R)salsolinol was proved to be selectively toxic to dopamine neurons and its level increased in parkinsonian CSF. The enzyme which determines the level of N-methyl( R)salsolinol, ( R)salsolinol N-methyltransferase, was found increased in the lymphocytes prepared from PD patients. The mechanism of dopamine cell death by N-methyl( R)salsolinol was studied in vitro. N-Methyl( R)salsolinol induced apoptosis in human dopaminergic neuroblastoma cells. It was suggested that in the mitochondria there is a molecule which interacts with N-methyl( R)salsolinol and initiates an apoptotic signal.
Maruyama
Wakako
W
Laboratory of Biochemistry and Metabolism, Department of Basic Gerontology, Institute for Longevity Sciences, Obu, Aichi, 474-8522, Japan. maruyama@nils.go.jp
Naoi
Makoto
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D002452:Cell Count; D004195:Disease Models, Animal; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism / Q000633:toxicity; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009498:Neurotoxins / Q000378:metabolism / Q000633:toxicity*; D018384:Oxidative Stress; D020734:Parkinsonian Disorders / Q000209:etiology* / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012490:Salsoline Alkaloids / Q000378:metabolism / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects; D044005:Tetrahydroisoquinolines; D014407:Tumor Cells, Cultured
D007546:Isoquinolines; D009498:Neurotoxins; D012490:Salsoline Alkaloids; D044005:Tetrahydroisoquinolines; C032837:salsoline