Gamma-enolase

Gamma-enolase (ENO2) is a glycolytic enzyme that catalyzes the interconversion of 2-phosphoglycerate and phosphoenolpyruvate in glycolysis and gluconeogenesis (UniProt: P09104). Beyond its metabolic role, the protein exhibits neurotrophic and neuroprotective functions, binding in a calcium-dependent manner to cultured neocortical neurons to promote cell survival.

ENO2 is expressed in the central nervous system and has been associated with neuronal protection and survival pathways. The protein's dual role as both a metabolic enzyme and a signaling molecule suggests involvement in neural homeostasis and energy metabolism coupling.

ENO2 is relevant to Alzheimer's Disease pathology. In human post-mortem AD brain tissue compared to age-matched controls, ENO2 was significantly down-regulated (mean log2 fold-change −0.33) as measured by TMT-labeled quantitative proteomics across subcellular fractions (Chaparral AD proteomics). The reduced expression of this neuroprotective glycolytic enzyme in AD brains may contribute to neuronal dysfunction and reduced metabolic resilience in the disease context.