Regulation of enolase activation to promote neural protection and regeneration in spinal cord injury

Neural Regen Res, 2023 · DOI: https://doi.org/10.4103/1673-5374.361539 · Published: July 1, 2023

Spinal Cord Injury Immunology Physiology

Simple Explanation

Spinal cord injury (SCI) leads to loss of function, mobility, and sensation, with no approved cure. The enzyme enolase, which increases after SCI, influences inflammation and recovery. Enolase normally resides inside cells, but after injury, it appears on the cell surface, activating glial cells and signaling pathways. This microglial activation promotes inflammation. An enolase inhibitor, ENOblock, may reduce glial cell activation and promote recovery by attenuating Rho-associated kinase activation and preventing the cleavage of a neurotrophic protein.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Enolase promotes both pro- and anti-inflammatory events and regulates functional recovery in SCI.
2
ENOblock attenuates the activation of Rho-associated kinase, which may decrease glial cell activation and promote functional recovery following SCI.
3
Inhibition of NSE is associated with decreased levels of Cat X, resulting in the attenuation of neuronal death

Research Summary

This review summarizes the important metabolic pathways involved in SCI as well as the importance of enolase activity on the cell surface following SCI. Interaction at the cell surface allows enolase to contribute to neuroinflammation and degeneration through the immune cell activation, the production of pro-inflammatory mediators, and the activation of cell signaling pathways. Enolase inhibition by ENOblock could also prevent NSE C-terminus cleavage by Cat X, giving rise to a fully functional, neurotrophic NSE.

Practical Implications

Therapeutic Target

Enolase activation and inhibition as a potential therapeutic target following SCI to promote neuronal survival and regeneration.

Drug Development

Development of drugs like ENOblock that can inhibit enolase activation and promote neuroprotection.

Combination Therapies

Investigation into combination strategies targeting several metabolic events following SCI and TBI to fully understand the therapeutic potential.

Study Limitations

1
Limited information is available on the role of enolase in neurodegeneration in SCI.
2
There is also limited information on the mechanisms by which enolase acts on the immune system following neuroinflammation.
3
Additional research is necessary to understand enolase activity and impact on SCI, as well as for strategic use in other neurodegenerative diseases.

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