Neuron specific enolase: a promising therapeutic target in acute spinal cord injury

Abstract

Enolase is a multifunctional protein, which is expressed abundantly in the cytosol. Upon stimulatory signals, enolase can traffic to cell surface and contribute to different pathologies including injury, autoimmunity, infection, inflammation, and cancer. Cell-surface expression of enolase is often detected on activated monocytes/macrophages, microglia and astrocytes, promoting extracellular matrix degradation, production of pro-inflammatory cytokines/chemokines, and invasion of inflammatory cells in the sites of injury and inflammation. Inflammatory stimulation also induces translocation of enolase from the cytosolic pool to the cell surface where it can act as a plasminogen receptor and promotes extracellular matrix degradation and tissue damage. Spinal cord injury (SCI) is a devastating debilitating condition whose progressive pathological changes include complex and evolving molecular cascades, and insights into the role of enolase in multiple inflammatory events have not yet been fully elucidated. Neuronal damage following SCI could be characterized by an elevation of neuron specific enolase (NSE), which is also known to play a role in the pathogenesis of hypoxic-ischemic brain injury. Thus, NSE is now considered as a biomarker in ischemic brain damage, and it has recently been suggested to be a biomarker in traumatic brain injury (TBI), stroke and anoxic encephalopathy after cardiac arrest and acute SCI as well. This review gives an overview of current basic research and clinical studies on the role of multifunctional enolase in neurotrauma, with a special emphasis on NSE in acute SCI.

Exercise and taurine in inflammation, cognition, and peripheral markers of blood-brain barrier integrity in older women

“…Low chronic systemic inflammation during aging, known as 'inflammaging', has been proposed to increase BBB permeability (Elwood et al 2017), which has been measured through peripheral levels of neuronalderived proteins, such as S100β and neuronal-specific enolase (NSE) (Marchi et al 2004, Sağ et al 2017). S100β protein is composed by two isometric subunits being expressed primarily by astrocytes and found predominately in astroglial and Scwann cells, while NSE is a 78kD gammahomodimer that represents the mainly enolase-enzyme found in neurons , Haque et al 2016. Quantitative measures of both biomarkers have been used to represent BBB permeability and neuronal damage in humans, respectively (Isgrò et al 2015, Dadas et al 2016.…”

Targeting Enolase in Reducing Secondary Damage in Acute Spinal Cord Injury in Rats

“…Enolase plays multiple roles in growth control, immune activation, inflammation, and allergic responses (4–8). Cell-surface expression of enolase is often detected on activated monocytes/macrophages, microglia, and astrocytes, which promotes degradation of extracellular matrix (ECM), production of pro-inflammatory cytokines/chemokines, and invasion of inflammatory cells in the sites of injury (2, 9–11). Upon activation, enolase can also act as a heat-shock protein by binding to cytoskeletal and chromatin structures, and may play crucial roles in a variety of injury, and pathophysiological processes (9, 12, 13).…”

Proteomic profiling of proteins in the dorsal horn of the spinal cord in dairy cows with chronic lameness

“…Non-glycolytic functions of metabolic enzymes have gained attention, in particular enolase, which can act as plasminogen receptor during pathological states [70]. Inflammatory signals promote enolase translocation to the cell membrane [71] enhancing plasminogen activation [72] and promoting extracellular matrix degradation, metalloproteinase activation, macrophage migration and cytokines synthesis [71,73]. Cell surface enolase has been found in neurons, activated microglia [74], astrocytes [73] and different immune cells [71].…”

“…Inflammatory signals promote enolase translocation to the cell membrane [71] enhancing plasminogen activation [72] and promoting extracellular matrix degradation, metalloproteinase activation, macrophage migration and cytokines synthesis [71,73]. Cell surface enolase has been found in neurons, activated microglia [74], astrocytes [73] and different immune cells [71]. The role of enolase in chronic pain was confirmed by Polcyn et al (2017) [75], after selectively blocking its non-glycolytic functions, thus reducing spinal glial activation and cytokine synthesis in a rat model of spinal cord injury.…”