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N-Methyl-(R)salsolinol as a dopaminergic neurotoxin: From an animal model to an early marker of Parkinson’s disease

  • M. Naoi
  • W. Maruyama
  • P. Dostert
  • Y. Hashizume
Part of the Journal of Neural Transmission. Supplementa book series (NEURAL SUPPL, volume 50)

Summary

A dopamine-derived 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydrosioquinoline [N-methyl-(R)salsolinol] was found to occur enantio-selectively in human brain. This isoquinoline induced parkinsonism in rat after injection in the striatum, and the behavioral, biochemical and pathological changes were very similar to those in Parkinson’s disease. N-Methyl-(R)salsolinol depleted dopamine neurons in the rat substantia nigra without necrotic tissue reaction, which may be due to the apoptotic death process, as proved by its induction of DNA damage in dopaminergic neuroblastoma SH-SY5Y cells. N-Methyl-(R)salsolinol was found to increase significantly in the cerebrospinal fluid of parkinsonian patients. All these results suggest that N-methyl-(R)salsolinol may be an endogenous neurotoxin to cause Parkinson’s disease and the enzymes involved in its biosynthesis and catabolism may be endogenous factors in the pathogenesis of this disease.

Keywords

Tyrosine Hydroxylase Substantia Nigra Dopamine Neuron Pyruvic Acid Parkinsonian Patient 
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 1997

Authors and Affiliations

  • M. Naoi
    • 1
  • W. Maruyama
    • 2
  • P. Dostert
    • 3
  • Y. Hashizume
    • 4
  1. 1.Department of BiosciencesNagoya Institute of TechnologyNagoyaJapan
  2. 2.Department of NeurologyNagoya University School of MedicineNagoyaJapan
  3. 3.Research and DevelopmentPharmacia and UpjohnMilanItaly
  4. 4.Institute for Medical Science of AgingAichi Medical UniversityAichiJapan

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