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Background
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Glyceraldehyde 3-phosphate dehydrogenase (GAPDH or G3PDH) is an enzyme of 37 kDa that is consisdered as a cellular enzyme involved in glycolysis. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a pleiotropic enzyme that is overexpressed in apoptosis and in several human chronic pathologies. Its role as a mediator for cell death has also been highlighted. At the molecular level, sequential steps lead to nuclear translocation of GAPDH during cell death as follows: first, a catalytic cysteine in GAPDH (C150 in rat GAPDH) is S-nitrosylated by nitric oxide (NO) that is generated from inducible nitric oxide synthase (iNOS) and/or neuronal NOS (nNOS), second, the modified GAPDH becomes capable of binding with Siah1, an E3 ubiquitin ligase, and stabilizes it, third, the GAPDH-Siah protein complex translocates to the nucleus, dependent on Siah1's nuclear localization signal, and degrades Siah1's substrates in the nucleus, which results in cytotoxicity. A recent report suggests that GAPDH may be genetically associated with late-onset of Alzheimer's disease. (?)-deprenyl, which has originally been used as a monoamine oxidase inhibitor for Parkinson's disease, binds to GAPDH and displays neuroprotective actions.
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