New Insights into the Role of Neuron-Specific Enolase in Neuro-Inflammation, Neurodegeneration, and Neuroprotection

Azizul Haque, Rachel Polcyn, Denise Matzelle, Naren L Banik, Azizul Haque, Rachel Polcyn, Denise Matzelle, Naren L Banik

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.

Keywords: cathepsin X; degeneration; gliosis; neuron specific enolase (NSE); neuroprotection; spinal cord injury (SCI).

Conflict of interest statement

The authors have no financial conflicts of interest.

Figures

Figure 1
Figure 1
Elevation of enolase promotes glycolysis, cellular proliferation, activation and migration via the PI3K/AKT and MAPK/ERK pathways. Enolase-mediated activation of PI3K also regulates RhoA kinase, which influences actin cytoskeleton reorganization, induction of neurite outgrowth, and growth arrest in neuronal cells. NSE is a substrate of Cat X, and regulation of NSE by Cat X may determine neuronal survival during CNS injury. Treatment with enolase inhibitor, ENOblock, may attenuate NSE, Cat X, and other inflammatory events in SCI, thus reducing neuroinflammation and neurodegeneration and promoting neuronal survival and/or neuroprotection.

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Source: PubMed

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