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Neurotoxins induce apoptosis in dopamine neurons: protection by N-propargylamine-1(R)- and (S)-aminoindan, rasagiline and TV1022

  • W. Maruyama
  • Y. Akao
  • M. B.H. Youdim
  • M. Naoi
Conference paper

Summary

In Parkinson’s disease, apoptosis was proposed to cause cell death in nigral dopamine neurons. An endogenous dopaminergic neurotoxin, N-methyl(R)salsolinol, stereo-selectively induced apoptosis in human neuroblastoma SH-SY5Y cells. In this paper the intracellular mechanism of apoptosis was studied using N-methyl(R)salsolinol, 6-hydroxydopamine and peroxynitrite as inducers of apoptosis. Apoptotic cascade was initiated by opening of mitochondrial permeability transition pore, as shown by collapse of mitochondrial membrane potential, AtPm. Apoptosis was executed by caspase 3 activation, followed by DNA fragmentation, which was antagonized by overexpressed Bc1-2. Propargylamines were found to protect the cells from apoptosis, and rasagiline, a selective irreversible inhibitor of type B monoamine oxidase was the most potent to prevent the cell death. Rasagiline preserved O’Pm, which was proved also in isolated mitochondria, and rasagiline completely suppressed the activation of caspases and DNA fragmentation. These results suggest that mitochondria regulate apoptotic process, which may be a target of neuroprotection by rasagiline.

References

Keywords

Apoptotic Cell Death Mitochondrial Membrane Potential Dopamine Neuron Mitochondrial Permeability Transition Pore Reactive Nitrogen Species 
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

  • W. Maruyama
    • 1
  • Y. Akao
    • 2
  • M. B.H. Youdim
    • 3
  • M. Naoi
    • 4
  1. 1.Department of Basic GerontologyNational Institute for Longevity SciencesJapan
  2. 2.Gifu International Institute of BiotechnologyMitakeGifuJapan
  3. 3.Technion-Israel Institute of Technology,Faculty of MedicineEve Topf and NPF Centers of Excellence for Neurodegenerative Diseases ResearchHaifaIsrael
  4. 4.Department of Brain SciencesInstitute of Applied BiochemistryGifuJapan

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