Regulatory mechanisms and targeted therapeutic strategies of glycolytic metabolism in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease where glycolytic metabolism plays a crucial role in its pathogenesis. This paper delves into the characteristics, key roles, and potential therapeutic applications of glycolytic metabolism in RA. In the synovial tissues and immune cells of RA patients, glycolytic metabolism is frequently observed to be enhanced, with key enzymes such as HK2, PFK-1/PFKFB3, and PKM2 showing abnormal expression and activation. Lactate, the end product of glycolysis, is increasingly recognized as an active signaling molecule that may contribute to the maintenance of inflammation and tissue destruction through multiple proposed mechanisms. Abnormal glycolytic metabolism in immune cells (macrophages, T cells, B cells, DCs) and synoviocytes (fibroblast-like synoviocytes, osteoclasts) respectively promote inflammatory responses and joint damage. Intervention strategies targeting glycolytic metabolism, such as the use of inhibitors for HK, PKM2, LDH, and PFK-1, have been proposed. However, numerous unresolved issues remain, necessitating further basic research to clarify the regulatory mechanisms and intercellular interactions of glycolytic metabolism, as well as in-depth studies on the clinical application value of related biomarkers.