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

Yukihiko Akao, Yoshihito Nakagawa, Wakako Maruyama, Tsutomu Takahashi, Makoto Naoi

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

An endogenous neurotoxin, N-methyl(R)salsolinol, has been proved to be involved in the pathogenesis of Parkinson's disease. Increased level of N- methyl(R)salsolinol in the cerebrospinal fluid and high activity of its synthesizing (R)salsolinol N-methyltransferase in lymphocytes were confirmed in the majority of parkinsonian patients. Recently this neurotoxin was found to induce apoptosis in human dopaminergic neuroblastoma SH-SY5Y cells. In this study, we tried to elucidate the intracellular mechanism of apoptosis induced by N-methyl(R)salsolinol, and proved activation of caspase 3 after incubation with this toxin by Western blot analysis. Further, a caspase 3 inhibitor, acetyl-L-aspartyl-L-glutamyl-L-valyl-L-aspartic aldehyde, prevented the 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 Parkinson's disease.

Original languageEnglish
Pages (from-to)153-156
Number of pages4
JournalNeuroscience Letters
Volume267
Issue number3
DOIs
Publication statusPublished - 04-06-1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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