Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Neuroprotection by pharmacologic blockade of the GAPDH death cascade.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) participates in a cell death cascade wherein a variety of stimuli activate nitric oxide (NO) synthases with NO nitrosylating GAPDH, conferring on it the ability to bind to Siah, an E3-ubiquitin-ligase, whose nuclear localization signal enables the GAPDH/Siah protein complex to translocate to the nucleus where degradation of Siah targets elicits cell death. R-(-)-Deprenyl (deprenyl) ameliorates the progression of disability in early Parkinson's disease and also has neuroprotective actions. We show that deprenyl and a related agent, TCH346, in subnanomolar concentrations, prevent S-nitrosylation of GAPDH, the binding of GAPDH to Siah, and nuclear translocation of GAPDH. In mice treated with the dopamine neuronal toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), low doses of deprenyl prevent binding of GAPDH and Siah1 in the dopamine-enriched corpus striatum.

Pubmed ID: 16505364


  • Hara MR
  • Thomas B
  • Cascio MB
  • Bae BI
  • Hester LD
  • Dawson VL
  • Dawson TM
  • Sawa A
  • Snyder SH


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 7, 2006

Associated Grants

  • Agency: NIDA NIH HHS, Id: DA-00074
  • Agency: NIDA NIH HHS, Id: DA-00266
  • Agency: NIMH NIH HHS, Id: MH-069853
  • Agency: NINDS NIH HHS, Id: NS-38377

Mesh Terms

  • Animals
  • Antiparkinson Agents
  • Apoptosis
  • Cell Line
  • Glyceraldehyde-3-Phosphate Dehydrogenases
  • Humans
  • In Vitro Techniques
  • MPTP Poisoning
  • Male
  • Mice
  • Nerve Degeneration
  • Neuroprotective Agents
  • Nitric Oxide
  • Nuclear Proteins
  • Oxepins
  • Parkinson Disease
  • Selegiline
  • Ubiquitin-Protein Ligases