脊髓损伤
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Figure 1｜Regulation of enolase activation may prevent neurodegeneration.
Recent studies have shown NSE inhibition to be a potential treatment strategy for SCI (Haque et al., 2016; Polcyn et al., 2020). ENOblock, an enolase inhibitor, alters inflammatory metabolic factors, chemokines, and cytokines following SCI in rat contusion models (Haque et al., 2018). Attenuation of the Rho/ROCK signaling pathway by NSE inhibition decreases the inflammatory response due to decreased glial cell activation and differentiation into pro-inflammatory phenotypes (Nakagawa et al., 1996; Mueller et al., 2005; Zhang et al., 2013; Haque et al., 2018). Ongoing studies in our laboratory suggest the inhibition of NSE by ENOblock attenuates Rho A/ROCK II in BV-2 microglia cell lines (Figure 1A), which in turn may inhibit M1 microglia/A1 astrocytes and attenuate inflammation and neurodegeneration, as well as promote repair by M2 microglia/A2 astrocytes. The exact mechanism by which ENOblock inhibits NSE is unknown, but there is reason to believe ENOblock inhibits the pro-death aspects of enolase, giving room for the pro-survival aspects.
Studies performed in our laboratory also show that NSE inhibition by ENOblock decreases Cat X expression in VSC4.1 motoneuron cells (Figure 1B). Enolase inhibition also protects neuronal cells (Figure 1C). These unpublished data support in favor of earlier findings that decreased Cat X levels may prevent cleavage of the C-terminal end of NSE, resulting in neural survival and axonal protection. Overall, ENOblock decreases neurodegeneration and improves neural survival and protection of axons by the inhibition of NSE and Cat X activation following SCI as shown in Figure 2. The combined aspects of ENOblock inhibition of enolase/NSE activation produce a perfect environment for neural regeneration to occur. Enolase inhibition attenuates the ROCK activation pathway and inhibits Cat X cleavage of NSE as shown in the diagram (Figure 2A and B), leading to neuron regeneration and survival.