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Modulation of control mechanisms of dopamine-induced apoptosis — a future approach to the treatment of Parkinson’s disease?

  • I. Ziv
  • D. Offen
  • A. Barzilai
  • R. Haviv
  • R. Stein
  • R. Zilkha-Falb
  • A. Shirvan
  • E. Melamed
Conference paper

Summary

The cause for the progressive and selective degeneration of the dopaminergic (DA) nigrostriatal neurons in Parkinson’s disease (PD) is still unknown. We suggest a novel approach, that links this neuronal degenerative process to inappropriate triggering of apoptosis, an active, controlled program of cellular self destruction, by excess oxidative stress mediated by DA metabolism. In support of this concept, we found that DA, the endogenous neurotransmitter, is capable of initiating apoptosis in cultured, postmitotic chick sympathetic neurons, an observation further extended to other cellular systems (PC-12 cells, cerebellar granular cells, thymocytes, splenocytes). In comparing the relative apoptosis-triggering potency of other mononamine neurotransmitters, DA was found to be the most active, whereas norepinephrine and serotonin had a moderate and a mild effects, respectively. This grading can be correlated with the relative involvement of the relevant neuronal systems (i.e., substantia nigra, locus ceruleus and raphe nuclei) in PD.

Keywords

Nerve Growth Factor Locus Ceruleus Growth Factor Deprivation Nigrostriatal Neuron Endogenous Neurotransmitter 
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

  • I. Ziv
    • 1
  • D. Offen
    • 1
  • A. Barzilai
    • 2
  • R. Haviv
    • 2
  • R. Stein
    • 2
  • R. Zilkha-Falb
    • 2
  • A. Shirvan
    • 1
  • E. Melamed
    • 1
  1. 1.Department of NeurologyBeilinson Medical CenterPetah-TiqvaIsrael
  2. 2.Department of Biochemistry, The George Wise Faculty of Life Sciences, NeuroscienceTel-Aviv UniversityTel-AvivIsrael

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