| 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
(Affiliation: Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA. william.tatton at mssm.edu)
|
| Journal | Journal of neural transmission (Vienna, Austria : 1996)
(J Neural Transm)
Vol. 110
Issue 5
Pg. 509-15
(May 2003)
ISSN: 0300-9564 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
- Selegiline
- propargylamine
- 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
|
