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.
Authors	W Tatton, R Chalmers-Redman, N Tatton
Journal	Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 110 Issue 5 Pg. 509-15 (May 2003) ISSN: 0300-9564 [Print] Austria
PMID	12721812 (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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