Apoptosis induced by an endogenous neurotoxin, N-methyl(R)salsolinol, is mediated by activation of caspase 3

An endogenous neurotoxin, N-methyl(R)salsolinol, has been proved to be invo lved in the pathogenesis of Parkinson's disease. Increased level of N-methy l(R)salsolinol in the cerebrospinal fluid and high activity of its synthesi zing (R)salsolinol N-methyltransferase in lymphocytes were confirmed in the majority of parkinsonian patients. Recently this neurotoxin was found to i nduce apoptosis in human dopaminergic neuroblastoma SH-SY5Y cells. In this study, we tried to elucidate the intracellular mechanism of apoptosis induc ed by N-methyl(R)salsolinol, and proved activation of caspase 3 after incub ation with this toxin by Western blot analysis. Further, a caspase 3 inhibi tor, acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspartic aldehyde, prevented th e nucleosomal DNA fragmentation completely. These results demonstrate that caspase 3 mediates apoptosis induced by an endogenous neurotoxin, N-methyl( R)salsolinol, which may cause apoptotic cell death of dopamine neurons in P arkinson's disease. (C) 1999 Elsevier Science ireland Ltd. All rights reser ved.