Neural Regeneration Research ›› 2025, Vol. 20 ›› Issue (on line): 1-15.

   

Metabolic reprogramming of astrocytes: emerging roles of lactate

Zeyu Liu1 , Yijian Guo2 , Ying Zhang1 , Yulei Gao1, *, Bin Ning1, 2, *   

  1. 1 Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong Province, China; 2 Department of Spinal Surgery, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China
  • Online:2025-01-01 Published:2024-12-18
  • Contact: Bin Ning, MD, bning@sdfmu.edu.cn; Yulei Gao, MD, gaoyulei202111@163.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, Nos. 82071383, 82371392 (to BN); the Natural Science Foundation of Shandong Province of China (Key Project), No. ZR2020KH007 (to BN); “Taishan Scholar Distinguished Expert Program” of Shandong Province, No. tstp20231257 (to BN); Health Commission Science and Technology Plan Project of Jinan, No.2023-1-8 (to YZ).

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Abstract: 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.

Key words: astrocyte, epigenetic modifications, inflammation, lactate, lactylation, metabolic, plasticity, regeneration, treatment