Anti-Apoptotic Function of Propargylamines

  • Wakako Maruyama
  • Alan A. Boulton
  • Moussa B. H. Youdim
  • Makoto Naoi
Part of the Advances in Behavioral Biology book series (ABBI, volume 53)

Abstract

(-)Deprenyl (selegiline), an inhibitor specific to type B monoamine oxidase (MAO-B), is now clinically applied for Parkinson’s disease (PD), as an adjunct of L-DOPA therapy. Recent results have shown that selegiline (Parkinson Study Group, 1989) and structurally related propargylamines, such as (R)(+)-N-propargyl-1-aminoindan (rasagiline) and (R)-N-(2-heptyl)-N-methylpropargylamine (R-2HMP), delay the progress of the disease. However, it remains to be clarified, whether the effects are due to the neuroprotective or neurorescue effects, or only symptomatic. On the other hand, the well-controlled apoptotic cascade has been proposed to be a target of neuroprotection (Thompson, 1995), even though it requires further evidence whether apoptosis is a major type of cell death in PD (Jellinger, 2000). To elucidate this point, the mechanism underlying neuroprotection by propargylamines was examined using a cell model of apoptosis induced by endogenous N-methyl(R)salsolinol [NM(R)Sal] and peroxynitrite generating N-morpholino-sydnonimine (SIN-1) in human dopaminergic SH-SY5Y cells.

Keywords

Apoptotic Cascade Parkinson Study Group Peroxynitrite Generate Endogenous Neurotoxin Multicenter Control Clinical Trial 
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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References

  1. Akao, Y., Nakagawa, Y., Maruyama, W., Takahashi, T., Naoi, M., 1999, Apoptosis induced by endogenous neurotoxin, N-methyl(R)salsolinol, is mediated by activation of caspase 3. Neurosci. Lett., 267: 153–156.PubMedCrossRefGoogle Scholar
  2. Bronzetti, E., Felci, L., Ferrante, F., and Vasecchi, B., 1992, Effect of ethylene mustard aziridinium (AF64A) and of monoamine oxidase-B-inhibitor 1-deprenyl on the morphology of the rat hippocampus. Int. J. Tissue React., 14: 175–181.PubMedGoogle Scholar
  3. Carrilo, C. M., Minami, C. Kitani, K., Maruyama, W., Ohashi, K., Yamamoto, Y., Naoi, M., Kanai, S., and Youdim, M. B. H., 2000, Enhancing effect of rasagiline on superoxide dismutase and catalase activities in the dopaminergic system in rat. Life Sci. 67: 577–585.CrossRefGoogle Scholar
  4. Finnegan, K. T., Skratt, J. J., Irwin, I., DeLanney, L. E., and Langston, J. W., 1990, Protection against DSP-4 induced neurotoxicity by deprenyl is not related to its inhibition of MAAO B. Eur. J. Pharmacol., 184: 119–126.PubMedCrossRefGoogle Scholar
  5. Jellinger, K. A., 2000, Cell death mechanisms in Parkinson’s disease. J. Neural Transm. 107: 1–29.PubMedCrossRefGoogle Scholar
  6. Kitani, K., Kanai, S., Ivy, G. O., and Carrillo, M. C., 1998, Assessing the effects of deprenyl on longevity and antioxidant defenses in different animal models. Ann. N.Y. Acad. Sci. 854: 290–306.CrossRefGoogle Scholar
  7. Kitani, K., Minami, C., Maruyama, W., Kanai, S., Ivy, G. O., and Carrillo, M-C., 2000, Common properties for propargylamines of enhancing superoxide dismutase and catalase activities in the dopaminergic system in the rat: implications for the life prolonging effect of (-)deprenyl. J. Neural Transm. (Suppl) 60, 139–156.Google Scholar
  8. Maruyama, W., Yamamoto, T., Kitani, K., Carrillo, M. C., Youdim, M., and Naoi, M., 2000b, Mechanism underlying anti-apoptotic activity of a (-)deprenyl-related propargylamine, rasagiline. Mech. Aging Dev. 116:181–191.PubMedCrossRefGoogle Scholar
  9. Maruyama, W., Akao, Y., Youdim, M., and Naoi, M., 2001b, Neurotoxin induced apoptosis in dopamine neurons: protection by N-propargylamine-l(R)- and (S)-aminoindan, rasagiline and TV 1022. J. Neural Transm. 108: 11–24.PubMedCrossRefGoogle Scholar
  10. Maruyama, W., Boulton, A. A., Davis, B. A., Dostert, P., and Naoi. M., 2001b, Enantio-specific induction of apoptosis by an endogenous neurotoxin, N-methyl(R)salsolinol, in dopaminergic SH-SY5Y cells: Suppression of apoptosis by N-(2-heptyl)-N-methylpropargylamine J. Neural Transm. 108:11–24.PubMedCrossRefGoogle Scholar
  11. Maruyama, W., Akao, Y., Youdim, M. B. H., Davis, B. A., and Naoi, M., 2001c, Transfection-enforced Bcl-2 overexpression and an anti-Parkinson drug, rasagiline, prevent nuclear accumulation of glyceraldehyde-3-phosphate dehydrogenase induced by an endogenous- dopaminergic neurotoxin, N-methyl(R)salsolinol. J. Neurochem. In press.Google Scholar
  12. Naoi, M. and Maruyama, W., 1999, Af-Methyl(R)salsolinol, a dopamine neurotoxin in Parkinson’s disease. Adv. Neurol, 180: 259–264.Google Scholar
  13. Naoi, M., and Maruyama, W., Models of Parkinson’s disease, “Catecholamine Research: From Molecular Insights to Clinical Medicine”, KLUWER ACADEMIC/PLENUM PUBLISHERS, New York, In press.Google Scholar
  14. Parkinson Study Group, 1989, DATATOP: A multicenter controlled clinical trial in early Parkinson’s Disease. Arch. Neurol. 46: 1052–1060.CrossRefGoogle Scholar
  15. Tatton, W. G. and Greenwood, C. E., 1991, Rescue of dying neurons: a new action of deprenyl in MPTP parkinsonism. J. Neurosci. Res., 30: 666–672.PubMedCrossRefGoogle Scholar
  16. Thompson C. B., 1995, Apoptosis in the pathogenesis and treatment of diseases. Science, 267: 1456–1462.PubMedCrossRefGoogle Scholar
  17. Tsujimoto, Y and Shimizu, S., 2000, Bcl-2 family: Life-or-death switch. FEBS Lett. 466, 6–10.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Wakako Maruyama
    • 1
  • Alan A. Boulton
    • 2
  • Moussa B. H. Youdim
    • 3
  • Makoto Naoi
    • 4
  1. 1.National Institute for Longevity SciencesAichiJapan
  2. 2.University of SaskatchewanSaskatoonCanada
  3. 3.Technion-Israel Institute Technology Faculty of MedicineHaifaIsrael
  4. 4.Institute of Applied BiochemistryGifuJapan

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