Glyceraldehyde-3-phosphate dehydrogenase in neurodegeneration and apoptosis signaling

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a well-studied glycolytic enzyme that plays a key role in energy metabolism. GAPDH catalyzes the conversion of glyceraldehyde-3-phosphate to 1,3-bisphosphoglycerate in the glycolytic pathway. As part of the conversion, GAPDH converts NAD+ to the high-energy electron carrier NADH. GAPDH has been referred to as a "housekeeping" protein and based on the view that GAPDH gene expression remains constant under changing cellular conditions, the levels of GAPDH mRNA have frequently been used to normalize northern blots. In recent years, that view has changed since GAPDH is now known to contribute to a number of diverse cellular functions unrelated to glycolysis. Normative functions of GAPDH now include nuclear RNA export, DNA replication, DNA repair, exocytotic membrane fusion, cytoskeletal organization and phosphotransferase activity. Pathologically, GAPDH has been implicated in apoptosis, neurodegenerative disease, prostate cancer and viral pathogenesis (see Sirover (1999) for a recent review of GAPDH functions). Most recently, it has been shown that GAPDH is a target for deprenyl related compounds (Carlile et al., 2000; Kragten et al., 1998) and may contribute to the neuroprotection offered by those compounds.