Targeting Glycolysis for Spinal Cord Injury: Regulatory Mechanisms and Therapeutic Prospects.

Abstract

Spinal cord injury (SCI) is a severe neurological disorder that not only causes significant physical and psychological harm to patients but also imposes a substantial economic burden on families and society. Following SCI, a cascade of secondary events occurs, including inflammatory responses, scar formation, and mitochondrial dysfunction. Numerous studies have demonstrated that glycolysis plays a crucial role in the pathophysiological changes post-SCI and may serve as a promising therapeutic target for future SCI treatments. This account systematically summarizes the alterations in glycolysis after SCI, focusing on three key aspects: the activation pathways of glycolysis, changes in metabolic rates and metabolites, and the expression levels of related enzymes and molecules. Furthermore, it highlights the mechanisms by which glycolysis-targeted interventions promote SCI repair, including modulation of inflammatory responses, oxidative stress, apoptosis, and axonal regeneration. Additionally, the applications and limitations of glycolysis-targeting drugs and other emerging therapeutic approaches are critically analyzed. Finally, this review outlines preliminary achievements and prospects in the clinical translation of glycolysis-targeted therapies for SCI. This review summarizes the mechanisms underlying the regulation of glycolysis-targeting SCI, along with current major therapeutic strategies and associated challenges, thereby offering potential insights into the treatment of SCI.