Proapoptotic protein glyceraldehyde-3-phosphate dehydrogenase: a possible site of action of antiapoptotic drugs

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been recognized as a classical glycolytic protein and has been used as a “housekeeping” gene in studies of genetic expression and regulation. However, recent advances reveal that GAPDH displays diverse nonglycolytic functions depending on its subcellular localization. Among those functions, one of the most intriguing is likely to be the induction of apoptosis. Previous works by our group and others have demonstrated that the overexpression of GAPDH and its subsequent nuclear translocation appear to be implicated in the initiation of one or more apoptotic cascades and also in the etiology of some neurological diseases. This review addresses new data demonstrating that a protein, referred to as proapoptotic protein GAPDH, with a quite mundane function in healthy cells behaves very differently during cell suicide, and summarizes emphatically the importance of this protein as a putative molecular target in developing antiapoptotic therapeutic agents for the treatment of certain neurodegenerative disorders.