Glycolysis Rate-Limiting Enzymes: Novel Potential Regulators of Rheumatoid Arthritis Pathogenesis

• Published in: Frontiers in immunology Vol. 12; p. 779787
• Main Authors: Zuo, Jianlin, Tang, Jinshuo, Lu, Meng, Zhou, Zhongsheng, Li, Yang, Tian, Hao, Liu, Enbo, Gao, Baoying, Liu, Te, Shao, Pu
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 24.11.2021
• Subjects: Animals; Antirheumatic Agents - therapeutic use; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - enzymology; Arthritis, Rheumatoid - immunology; Carrier Proteins - antagonists & inhibitors; Carrier Proteins - metabolism; Enzyme Inhibitors - therapeutic use; Enzymes - metabolism; Glucose - metabolism; glycolysis; Glycolysis - drug effects; Hexokinase - antagonists & inhibitors; Hexokinase - metabolism; Humans; Immunology; Joints - drug effects; Joints - enzymology; Joints - immunology; Kinetics; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - metabolism; pathogenesis; Phosphofructokinase-1 - antagonists & inhibitors; Phosphofructokinase-1 - metabolism; Phosphofructokinase-2 - antagonists & inhibitors; Phosphofructokinase-2 - metabolism; rate-limiting enzymes; rheumatoid arthritis; Thyroid Hormone-Binding Proteins; Thyroid Hormones - metabolism; pathogenesis; rate-limiting enzymes; rheumatoid arthritis; glycolysis; RA
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.779787

Rheumatoid arthritis (RA) is a classic autoimmune disease characterized by uncontrolled synovial proliferation, pannus formation, cartilage injury, and bone destruction. The specific pathogenesis of RA, a chronic inflammatory disease, remains unclear. However, both key glycolysis rate-limiting enzymes, hexokinase-II (HK-II), phosphofructokinase-1 (PFK-1), and pyruvate kinase M2 (PKM2), as well as indirect rate-limiting enzymes, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), are thought to participate in the pathogenesis of RA. In here, we review the latest literature on the pathogenesis of RA, introduce the pathophysiological characteristics of HK-II, PFK-1/PFKFB3, and PKM2 and their expression characteristics in this autoimmune disease, and systematically assess the association between the glycolytic rate-limiting enzymes and RA from a molecular level. Moreover, we highlight HK-II, PFK-1/PFKFB3, and PKM2 as potential targets for the clinical treatment of RA. There is great potential to develop new anti-rheumatic therapies through safe inhibition or overexpression of glycolysis rate-limiting enzymes.