Liu Zeyu, Guo Yijian, Zhang Ying, Gao Yulei, Ning Bin
Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China.
Department of Spinal Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.
Neural Regen Res. 2026 Feb 1;21(2):421-432. doi: 10.4103/NRR.NRR-D-24-00776. Epub 2024 Dec 16.
Lactate serves as a key energy metabolite in the central nervous system, facilitating essential brain functions, including energy supply, signaling, and epigenetic modulation. Moreover, it links epigenetic modifications with metabolic reprogramming. Nonetheless, the specific mechanisms and roles of this connection in astrocytes remain unclear. Therefore, this review aims to explore the role and specific mechanisms of lactate in the metabolic reprogramming of astrocytes in the central nervous system. The close relationship between epigenetic modifications and metabolic reprogramming was discussed. Therapeutic strategies for targeting metabolic reprogramming in astrocytes in the central nervous system were also outlined to guide future research in central nervous system diseases. In the nervous system, lactate plays an essential role. However, its mechanism of action as a bridge between metabolic reprogramming and epigenetic modifications in the nervous system requires future investigation. The involvement of lactate in epigenetic modifications is currently a hot research topic, especially in lactylation modification, a key determinant in this process. Lactate also indirectly regulates various epigenetic modifications, such as N6-methyladenosine, acetylation, ubiquitination, and phosphorylation modifications, which are closely linked to several neurological disorders. In addition, exploring the clinical applications and potential therapeutic strategies of lactic acid provides new insights for future neurological disease treatments.
乳酸作为中枢神经系统中的关键能量代谢物，促进大脑的基本功能，包括能量供应、信号传导和表观遗传调控。此外，它将表观遗传修饰与代谢重编程联系起来。尽管如此，这种联系在星形胶质细胞中的具体机制和作用仍不清楚。因此，本综述旨在探讨乳酸在中枢神经系统星形胶质细胞代谢重编程中的作用和具体机制。讨论了表观遗传修饰与代谢重编程之间的密切关系。还概述了针对中枢神经系统星形胶质细胞代谢重编程的治疗策略，以指导未来中枢神经系统疾病的研究。在神经系统中，乳酸起着至关重要的作用。然而，其作为神经系统中代谢重编程和表观遗传修饰之间桥梁的作用机制仍需未来研究。乳酸参与表观遗传修饰目前是一个热门研究课题，尤其是在乳酰化修饰方面，它是这一过程的关键决定因素。乳酸还间接调节各种表观遗传修饰，如N6-甲基腺苷、乙酰化、泛素化和磷酸化修饰，这些修饰与几种神经系统疾病密切相关。此外，探索乳酸的临床应用和潜在治疗策略为未来神经系统疾病治疗提供了新的见解。
