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J Neural Transm. 2003 May;110(5):509-15.

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

Author information

  • 1Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA. william.tatton@mssm.edu

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.

PMID:
12721812
[PubMed - indexed for MEDLINE]
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