Abstract
Neurodegeneration is a complex process that leads to irreversible neuronal damage and death in spinal cord injury (SCI) and various neurodegenerative diseases, which are serious, debilitating conditions. Despite exhaustive research, the cause of neuronal damage in these degenerative disorders is not completely understood. Elevation of cell surface α-enolase activates various inflammatory pathways, including the production of pro-inflammatory cytokines, chemokines, and some growth factors that are detrimental to neuronal cells. While α-enolase is present in all neurological tissues, it can also be converted to neuron specific enolase (NSE). NSE is a glycolytic enzyme found in neuronal and neuroendocrine tissues that may play a dual role in promoting both neuroinflammation and neuroprotection in SCI and other neurodegenerative events. Elevated NSE can promote ECM degradation, inflammatory glial cell proliferation, and actin remodeling, thereby affecting migration of activated macrophages and microglia to the injury site and promoting neuronal cell death. Thus, NSE could be a reliable, quantitative, and specific marker of neuronal injury. Depending on the injury, disease, and microenvironment, NSE may also show neurotrophic function as it controls neuronal survival, differentiation, and neurite regeneration via activation of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways. This review discusses possible implications of NSE expression and activity in neuroinflammation, neurodegeneration, and neuroprotection in SCI and various neurodegenerative diseases for prognostic and therapeutic potential.
Highlights
Enolase is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate
While the γγ form of Neuron specific enolase (NSE) is expressed in neurons, the αγ form is expressed in microglia, oligodendrocytes, and astrocytes [3,4,5]
Studies suggest that NSE, which is measurable in blood and cerebrospinal fluid, could be a potentially useful biomarker for assessing neuronal damage and the prognosis of brain injury [6,7,8,9,10]
Summary
Enolase is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. Our recent study suggests an inflammatory role for NSE in acute spinal cord injury (SCI), a devastating and debilitating condition with progressive pathological changes that include complex and evolving molecular cascades [22,23,24]. NSE-mediated activation of both PI3K and ERK1/2 pathways is required for neurite outgrowth, which may be attenuated by inhibition of MEK (MAPK/ERK kinase) and PI3K. This neurotrophic activity could be regulated by the cysteine protease, cathepsin X (Cat X), which cleaves the C-terminal end of the molecule and impairs its activity [26]. Pairing an improved understanding of these processes with novel and existing tools to enable effective regulation of NSE in neurons and glia might provide new opportunities for treatment of central nervous system (CNS) injury
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