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Neuroprotection by deprenyl and other propargylamines: glyceraldehyde-3-phosphate dehydrogenase rather than monoamine oxidase B.

Abstract
Deprenyl and other propargylamines are clinically beneficial in Parkinson's disease (PD). The benefits were thought to depend on monoamine oxidase B (MAO-B) inhibition. A large body of research has now shown that the propargylamines increase neuronal survival independently of MAO-B inhibition by interfering with apoptosis signaling pathways. The propargylamines bind to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The GAPDH binding is associated with decreased synthesis of pro-apoptotic proteins like BAX, c-JUN and GAPDH but increased synthesis of anti-apoptotic proteins like BCL-2, Cu-Zn superoxide dismutase and heat shock protein 70. Anti-apoptotic propargylamines that do not inhibit MAO-B are now in PD clinical trial.
AuthorsW Tatton, R Chalmers-Redman, N Tatton
JournalJournal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 110 Issue 5 Pg. 509-15 (May 2003) ISSN: 0300-9564 [Print] Austria
PMID12721812 (Publication Type: Journal Article, Review)
Chemical References
  • BAX protein, human
  • HSP70 Heat-Shock Proteins
  • Neuroprotective Agents
  • Propylamines
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-jun
  • bcl-2-Associated X Protein
  • propargylamine
  • Selegiline
  • Pargyline
  • Superoxide Dismutase
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Monoamine Oxidase
Topics
  • Animals
  • Apoptosis (drug effects)
  • Cell Survival (drug effects)
  • Glyceraldehyde-3-Phosphate Dehydrogenases (metabolism)
  • HSP70 Heat-Shock Proteins (metabolism)
  • Humans
  • Monoamine Oxidase (metabolism)
  • Neurons (drug effects, metabolism)
  • Neuroprotective Agents (pharmacology, therapeutic use)
  • Pargyline (analogs & derivatives, therapeutic use)
  • Parkinson Disease (drug therapy, metabolism)
  • Propylamines (therapeutic use)
  • Proto-Oncogene Proteins (metabolism)
  • Proto-Oncogene Proteins c-bcl-2 (metabolism)
  • Proto-Oncogene Proteins c-jun (metabolism)
  • Selegiline (pharmacology, therapeutic use)
  • Superoxide Dismutase (metabolism)
  • bcl-2-Associated X Protein

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