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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
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.


Neurosci Lett 1999 Jun 4;267(3):153-6
Akao Y, Nakagawa Y, Maruyama W, Takahashi T, Naoi M
Gifu International Institute of Biotechnology, Mitake, Japan.
PMID: 10380999, UI: 99308706

http://www.ncbi.nlm.nih.gov/PubMed/

janet paterson
52 now / 41 dx / 37 onset
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