Zhang Qi, Wang Sha-Sha, Zhang Zhao, Chu Shi-Feng
Basic medicine college, China Three Gorges University, Yichang, China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica & Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Cell Death Discov. 2025 Apr 6;11(1):149. doi: 10.1038/s41420-025-02453-5.
Microglia, the resident immune cells of the central nervous system, undergo metabolic reprogramming during neuroinflammation, playing a crucial role in the pathogenesis of neurological disorders such as Parkinson's disease. This review focuses on Pyruvate Kinase M2 (PKM2), a key glycolytic enzyme, and its impact on microglial metabolic reprogramming and subsequent neuroinflammation. We explore the regulatory mechanisms governing PKM2 activity, its influence on microglial activation and immune responses, and its contribution to the progression of various neurological diseases. Finally, we highlight the therapeutic potential of targeting PKM2 as a novel strategy for treating neuroinflammation-driven neurological disorders. This review provides insights into the molecular mechanisms of PKM2 in neuroinflammation, aiming to inform the development of future therapeutic interventions.
小胶质细胞是中枢神经系统中的常驻免疫细胞,在神经炎症过程中会发生代谢重编程,在帕金森病等神经疾病的发病机制中起关键作用。本综述聚焦于关键糖酵解酶丙酮酸激酶M2(PKM2)及其对小胶质细胞代谢重编程和后续神经炎症的影响。我们探讨了调控PKM2活性的机制、其对小胶质细胞活化和免疫反应的影响,以及其在各种神经疾病进展中的作用。最后,我们强调了将PKM2作为治疗神经炎症驱动的神经疾病的新策略的治疗潜力。本综述深入探讨了PKM2在神经炎症中的分子机制,旨在为未来治疗干预措施的开发提供依据。