Additionally, since GAPDH also interacts with disease-associated proteins, like huntingtin and the β-amyloid precursor protein (AβPP).

In particular, GAPDH has been reported to bind DNA and RNA, regulate transcription, possess kinase/phosphotransferase activity, catalyze microtubule formation and polymerization, facilitate vesicular transport, and bind integral membrane ion pumps associated with Ca 2+ release, as well as interact with a number of small molecules, including tumor necrosis factor (TNF)-α ribozymes, glutathione (GSH), p53, and nitric oxide (NO). However, recent research suggests that GAPDH possesses highly diverse, non-glycolytic functions, as its expression and activity are affected by multiple factors. Traditionally, GAPDH was used as a model, or control, in protein and gene structural- and catalytic mechanism-related studies, as well as a standard in Northern and Western blots because of its high degree of gene and protein sequence conservation across species. Research on the role of mammalian GAPDH in various biological signaling pathways over the last couple of decades has increased interest in this classical glycolytic enzyme. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) enzymes (EC 1.2.1.12) are a family of abundantly expressed oxidoreductases known for their role in glucose metabolism. In this review, we examine the many functions of GAPDH with respect to AD brain in particular, GAPDH’s apparent role(s) in AD-related apoptotic cell death is emphasized. Although, oxidative stress and damage is a common phenomenon in AD brain, it would seem that inhibition of glycolytic enzyme activity is merely one avenue in which AD pathology affects neuronal cell development and survival, as oxidative modification can also impart a toxic gain-of-function to many proteins, including GAPDH. Studies from our laboratory have shown significant inhibition of GAPDH dehydrogenase activity in Alzheimer disease (AD) brain due to oxidative modification. Specifically, GAPDH has been shown to interact with neurodegenerative disease-associated proteins, including the β-amyloid precursor protein (AβPP). that play important roles in normal and pathologic cell function. As a result of multiple isoforms and cellular locales, GAPDH is able to come in contact with a variety of small molecules, proteins, membranes, etc.

Recently, the oxidoreductase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), has become a subject of interest as more and more studies reveal a surfeit of diverse GAPDH functions, extending beyond traditional aerobic metabolism of glucose.

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