Abstract
An endogenous dopamine-derived N-methyl(R)salsolinol has been suggested to be involved in the pathogenesis of Parkinson's disease. In Parkinson's disease, the level of N-methyl(R)salsolinol increased in cerebrospinal fluid and the high activity of a synthesizing enzyme, (R)salsolinol N-methyltransferase, was detected in lymphocytes. This isoquinoline induced apoptotic DNA damage in human dopaminergic neuroblastoma SH-SY5Y cells. Among catechol isoquinolines, only N-methylsalsolinol induced apoptosis in the cells, and the scavengers of hydroxyl radicals and antioxidants suppressed DNA damage, suggesting that reactive oxygen species initiate apoptosis. The isoquinoline activated caspase-3 like proteases and a caspase-3 inhibitor protected the cells from DNA damge. (-)Deprenyl, but neither clorgyline nor pargyline, prevented apoptotic cell death. The mechanism of the protection was due to stabilization of mitochondrial membrane potential reduced by the toxin. In Parkinson's disease apoptosis may be induced in dopamine neurons by this endogenous neurotoxin, and (-)deprenyl may protect them from apoptotic death process.
| Original language | English |
|---|---|
| Pages (from-to) | 111-121 |
| Number of pages | 11 |
| Journal | Journal of Neural Transmission, Supplement |
| Issue number | 58 |
| Publication status | Published - 04-12-2000 |
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All Science Journal Classification (ASJC) codes
- Neurology
- Clinical Neurology
- Psychiatry and Mental health
- Biological Psychiatry
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Involvement of endogenous N-methyl(R)salsolinol in Parkinson's disease : Induction of apoptosis and protection by (-)deprenyl. / Naoi, M.; Maruyama, W.; Takahashi, T.; Akao, Y.; Nakagawa, Y.
In: Journal of Neural Transmission, Supplement, No. 58, 04.12.2000, p. 111-121.Research output: Contribution to journal › Article
TY - JOUR
T1 - Involvement of endogenous N-methyl(R)salsolinol in Parkinson's disease
T2 - Induction of apoptosis and protection by (-)deprenyl
AU - Naoi, M.
AU - Maruyama, W.
AU - Takahashi, T.
AU - Akao, Y.
AU - Nakagawa, Y.
PY - 2000/12/4
Y1 - 2000/12/4
N2 - An endogenous dopamine-derived N-methyl(R)salsolinol has been suggested to be involved in the pathogenesis of Parkinson's disease. In Parkinson's disease, the level of N-methyl(R)salsolinol increased in cerebrospinal fluid and the high activity of a synthesizing enzyme, (R)salsolinol N-methyltransferase, was detected in lymphocytes. This isoquinoline induced apoptotic DNA damage in human dopaminergic neuroblastoma SH-SY5Y cells. Among catechol isoquinolines, only N-methylsalsolinol induced apoptosis in the cells, and the scavengers of hydroxyl radicals and antioxidants suppressed DNA damage, suggesting that reactive oxygen species initiate apoptosis. The isoquinoline activated caspase-3 like proteases and a caspase-3 inhibitor protected the cells from DNA damge. (-)Deprenyl, but neither clorgyline nor pargyline, prevented apoptotic cell death. The mechanism of the protection was due to stabilization of mitochondrial membrane potential reduced by the toxin. In Parkinson's disease apoptosis may be induced in dopamine neurons by this endogenous neurotoxin, and (-)deprenyl may protect them from apoptotic death process.
AB - An endogenous dopamine-derived N-methyl(R)salsolinol has been suggested to be involved in the pathogenesis of Parkinson's disease. In Parkinson's disease, the level of N-methyl(R)salsolinol increased in cerebrospinal fluid and the high activity of a synthesizing enzyme, (R)salsolinol N-methyltransferase, was detected in lymphocytes. This isoquinoline induced apoptotic DNA damage in human dopaminergic neuroblastoma SH-SY5Y cells. Among catechol isoquinolines, only N-methylsalsolinol induced apoptosis in the cells, and the scavengers of hydroxyl radicals and antioxidants suppressed DNA damage, suggesting that reactive oxygen species initiate apoptosis. The isoquinoline activated caspase-3 like proteases and a caspase-3 inhibitor protected the cells from DNA damge. (-)Deprenyl, but neither clorgyline nor pargyline, prevented apoptotic cell death. The mechanism of the protection was due to stabilization of mitochondrial membrane potential reduced by the toxin. In Parkinson's disease apoptosis may be induced in dopamine neurons by this endogenous neurotoxin, and (-)deprenyl may protect them from apoptotic death process.
UR - http://www.scopus.com/inward/record.url?scp=0033678294&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033678294&partnerID=8YFLogxK
M3 - Article
C2 - 11128601
AN - SCOPUS:0033678294
SP - 111
EP - 121
JO - Journal of Neural Transmission, Supplement
JF - Journal of Neural Transmission, Supplement
SN - 0303-6995
IS - 58
ER -