Glyceraldehyde-3-phosphate dehydrogenase

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a 335-amino acid metabolic enzyme that catalyzes the conversion of glyceraldehyde 3-phosphate to 3-phospho-D-glyceroyl phosphate in glycolysis and gluconeogenesis (UniProt: P04406). Beyond its canonical glycolytic role, GAPDH possesses nitrosylase activity supporting nuclear functions including transcription, DNA replication, and apoptosis, and facilitates cytoskeletal organization and innate immune signaling through interactions with TRAF2 and TRAF3 (UniProt: P04406). The protein also assembles into the GAIT complex to regulate inflammatory gene translation in response to interferon-gamma.

GAPDH is upregulated in Alzheimer's disease brain tissue relative to age-matched controls, with a mean log2 fold-change of 0.32 across post-mortem TMT-labeled proteomics (Chaparral AD proteomics). This modest elevation was detected in subcellular fractions from human AD brain samples compared to healthy aging controls, suggesting dysregulation of glycolytic capacity or its non-canonical nuclear and inflammatory functions in the disease state.