Neuron specific enolase is a potential target for regulating neuronal cell survival and death: implications in neurodegeneration and regeneration

Enolase is a multifunctional enzyme primarily involved in catalyzing the conversion of 2phosphoglycerate to phosphoenolpyruvate during glycolysis and the reverse reaction during gluconeogenesis[1–4]. Though typically expressed in the cytosol, enolase has been shown to migrate to the cell surface upon inflammatory signal[3]. It then enhances antigen presentation for the invasion of host cells via plasminogen binding and subsequent plasmin activation, leading to degradation of the extracellular matrix. Cell surface expression of enolase, possibly due to an association with the urokinase-type plasminogen activator (uPA)/uPA receptor complex, additionally induces the production of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines [tumor necrotic factor (TNF)-α, interleukin (IL)-1β, interferon-γ, and transforming growth factor-β] and chemokines [monocyte chemotactic protein 1 and macrophage inflammatory protein (MIP)-1α] to augment neurodegenerative response[3,5]. Lysosomal proteases, especially cathepsins (e.g. Cathepsin X or Cat X), are instrumental in processing several neuronal proteins that generate either