Involvement of endogenous N-methyl(R)salsolinol in Parkinson's disease

Induction of apoptosis and protection by (-)deprenyl

M. Naoi, W. Maruyama, T. Takahashi, Y. Akao, Y. Nakagawa

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 languageEnglish
Pages (from-to)111-121
Number of pages11
JournalJournal of Neural Transmission, Supplement
Issue number58
Publication statusPublished - 04-12-2000
Externally publishedYes

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Selegiline
Parkinson Disease
Apoptosis
Caspase 3
DNA Damage
Isoquinolines
Clorgyline
Pargyline
Caspase Inhibitors
Mitochondrial Membrane Potential
Dopaminergic Neurons
Neurotoxins
Neuroblastoma
Hydroxyl Radical
Cerebrospinal Fluid
Reactive Oxygen Species
Dopamine
Peptide Hydrolases
Cell Death
Antioxidants

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

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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 journalArticle

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