中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (7): 1457-1462.doi: 10.4103/1673-5374.361539

• 综述:脊髓损伤修复保护与再生 • 上一篇    下一篇

调节烯醇化酶的激活促进脊髓损伤中的神经保护和再生

  


  • 出版日期:2023-07-15 发布日期:2023-01-11

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

Hannah M. McCoy1, Rachel Polcyn1, Naren L. Banik1, 2, 3, *, Azizul Haque1, 2, 3, *   

  1. 1Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA; 2Department of Neurosurgery, Medical University of South Carolina, Charleston, SC, USA; 3Ralph H. Johnson Veterans Administration Medical Center, Charleston, SC, USA
  • Online:2023-07-15 Published:2023-01-11
  • Contact: Naren L. Banik, PhD, baniknl@musc.edu; Azizul Haque, PhD, haque@musc.edu.
  • Supported by:
    This work was supported in part by funding from the Veterans Administration, Nos. 1IOBX001262 (to NLB), 1I01 BX004269 (to NLB and AH), South Carolina State Spinal Cord Injury Research Fund, No. SCIRF #2018 I-01 (to AH), funding from the National Institutes of Health, No. 1R21NS118393-01 (to NLB and AH), and Research Scientist Career Award from the Department of Veterans Affairs, No. 1K6BX 005964 (to NLB). 

摘要: https://orcid.org/0000-0001-9328-9365 (Naren L. Banik); https://orcid.org/0000-0002-6386-9390 (Azizul Haque)

Abstract: Spinal cord injury (SCI) is a debilitating condition characterized by damage to the spinal cord resulting in loss of function, mobility, and sensation with no U.S. Food and Drug Administration-approved cure. Enolase, a multifunctional glycolytic enzyme upregulated after SCI, promotes pro- and anti-inflammatory events and regulates functional recovery in SCI. Enolase is normally expressed in the cytosol, but the expression is upregulated at the cell surface following cellular injury, promoting glial cell activation and signal transduction pathway activation. SCI-induced microglia activation triggers pro-inflammatory mediators at the injury site, activating other immune cells and metabolic events, i.e., Rho-associated kinase, contributing to the neuroinflammation found in SCI. Enolase surface expression also activates cathepsin X, resulting in cleavage of the C-terminal end of neuron-specific enolase (NSE) and non-neuronal enolase (NNE). Fully functional enolase is necessary as NSE/NNE C-terminal proteins activate many neurotrophic processes, i.e., the plasminogen activation system, phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B, and mitogen-activated protein kinase/extracellular signal-regulated kinase. Studies here suggest an enolase inhibitor, ENOblock, attenuates the activation of Rho-associated kinase, which may decrease glial cell activation and promote functional recovery following SCI. Also, ENOblock inhibits cathepsin X, which may help prevent the cleavage of the neurotrophic C-terminal protein allowing full plasminogen activation and phosphatidylinositol-4,5-bisphosphate 3-kinase/mitogen-activated protein kinase activity. The combined NSE/cathepsin X inhibition may serve as a potential therapeutic strategy for preventing neuroinflammation/degeneration and promoting neural cell regeneration and recovery following SCI. The role of cell membrane-expressed enolase and associated metabolic events should be investigated to determine if the same strategies can be applied to other neurodegenerative diseases. Hence, this review discusses the importance of enolase activation and inhibition as a potential therapeutic target following SCI to promote neuronal survival and regeneration. 

Key words: cathepsin X, ENOblock, enolase, glia, mitogen-activated protein kinase/extracellular signal-regulated kinase, neurodegeneration, neuroinflammation, phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B, Rho-associated protein kinase, spinal cord injury