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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
Conference paper

Summary

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 Nmethyltransferase, 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 damage. (-)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.

Keywords

Mitochondrial Membrane Potential Multiple System Atrophy Dopamine Neuron Multiple System Atrophy Patient Dopaminergic Neurotoxin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Wien 2000

Authors and Affiliations

  • M. Naoi
    • 1
  • W. Maruyama
    • 2
  • T. Takahashi
    • 3
  • Y. Akao
    • 4
  • Y. Nakagawa
    • 5
  1. 1.Department of Brain SciencesInstitute of Applied BiochemistryMitake, GifuJapan
  2. 2.Department of Basic Gerontology, National Institute for Longevity SciencesLaboratory of Biochemistry and MetabolismObu, AichiJapan
  3. 3.Department of Food and NutritionAichi-Konan CollegeKonan, AichiJapan
  4. 4.Gifu International Institute of BiotechnologyMitake, GifuJapan
  5. 5.The Second Department of Internal MedicineOsaka Medical CollegeTakatsuki, OsakaJapan

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