中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (3): 1037-1057.doi: 10.4103/NRR.NRR-D-24-01412

• 综述:神经损伤修复保护与再生 • 上一篇    下一篇

作为神经系统疾病中突触功能调节剂的关键脂质

  

  • 出版日期:2026-03-15 发布日期:2025-07-02
  • 通讯作者: Yi Tang, PhD, tangyi@xwhosp.org; Zhiqing Xu, PhD, zhiqingx@ccmu.edu.cn; Qi Qin, PhD, qinqibao@126.com.
  • 基金资助:
    国家自然科学基金(82201568);首都健康促进与研究基金(2024-2-1031);北京市新星计划(20240484566)。

Regulation of synaptic function and lipid metabolism

Tongtong Zhang1 , Yunsi Yin1 , Xinyi Xia1 , Xinwei Que1 , Xueyu Liu2 , Guodong Zhao3 , Jiahao Chen4 , Qiuyue Chen4 , Zhiqing Xu4, *, Yi Tang1, 5, *, Qi Qin1, 5, *   

  1. 1 Department of Neurology & Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China;  2 Department of Neurology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China;  3 School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China;  4 Department of Pathology, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China;  5 National Center for Neurological Disorders, Beijing, China
  • Online:2026-03-15 Published:2025-07-02
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 82201568 (to QQ); Capital’s Funds for Health Improvement and Research, No. 2024-2-1031 (to QQ); Beijing Nova Program, No. 20240484566 (to QQ).

摘要:

突触是神经系统中传递信息的关键结构,其功能依赖于多种脂质的调节。脂质在突触形成、神经递质释放和信号传导中发挥重要作用,而脂质代谢失调与多种神经退行性疾病密切相关。近年来,脂质在突触功能和神经疾病中的复杂作用逐渐受到关注,但其具体机制尚未完全明确。此综述目的是探讨中枢神经系统中脂质如何调节突触活动,重点关注脂质在突触形成、神经递质释放和信号传导中的作用,并探讨胶质细胞通过脂质调节突触功能的机制。文章发现,在中枢神经系统中,脂质是细胞膜双分子层的重要组成部分,在突触结构和功能中发挥着关键作用,它可调节突触前的囊泡贩运、突触后的信号通路以及神经胶质细胞与神经元之间的相互作用。胆固醇能保持膜的流动性,促进脂质筏的形成。甘油磷脂有助于突触膜结构的完整性,并参与突触小泡的释放。鞘磷脂通过各种机制与突触受体相互作用,调节其活性,还参与炎症和细胞凋亡等细胞过程。脂肪酸对能量代谢和信号分子的合成至关重要。脂质代谢异常可能导致突触功能受损,从而影响神经元之间的信息传递和神经系统的整体健康,针对脂质代谢(尤其是通过调节胆固醇)的治疗策略有望改善这一状况。在神经退行性疾病(如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症)中,脂质代谢失调与突触功能障碍密切相关。因此,脂质既是神经再生和突触修复的关键分子,也可能在代谢失调时导致神经退行性病变。未来需要进一步要阐明脂质代谢与突触功能障碍之间的具体机制,并开发针对脂质代谢的精准治疗策略。

https://orcid.org/0000-0002-8052-065X (Yi Tang); https://orcid.org/0000-0002-0387-7559 (Zhiqing Xu);

https://orcid.org/0000-0002-3019-2061 (Qi Qin)

关键词: 星形胶质细胞, 中枢神经系统, 胆固醇, 甘油磷脂, 脂质, 小胶质细胞, 神经退行性疾病, 表鞘脂质, 突触, 治疗

Abstract: Synapses are key structures involved in transmitting information in the nervous system, and their functions rely on the regulation of various lipids. Lipids play important roles in synapse formation, neurotransmitter release, and signal transmission, and dysregulation of lipid metabolism is closely associated with various neurodegenerative diseases. The complex roles of lipids in synaptic function and neurological diseases have recently garnered increasing attention, but their specific mechanisms remain to be fully understood. This review aims to explore how lipids regulate synaptic activity in the central nervous system, focusing on their roles in synapse formation, neurotransmitter release, and signal transmission. Additionally, it discusses the mechanisms by which glial cells modulate synaptic function through lipid regulation. This review shows that within the central nervous system, lipids are essential components of the cell membrane bilayer, playing critical roles in synaptic structure and function. They regulate presynaptic vesicular trafficking, postsynaptic signaling pathways, and glial– neuronal interactions. Cholesterol maintains membrane fluidity and promotes the formation of lipid rafts. Glycerophospholipids contribute to the structural integrity of synaptic membranes and are involved in the release of synaptic vesicles. Sphingolipids interact with synaptic receptors through various mechanisms to regulate their activity and are also involved in cellular processes such as inflammation and apoptosis. Fatty acids are vital for energy metabolism and the synthesis of signaling molecules. Abnormalities in lipid metabolism may lead to impairments in synaptic function, affecting information transmission between neurons and the overall health of the nervous system. Therapeutic strategies targeting lipid metabolism, particularly through cholesterol modulation, show promise for treating these conditions. In neurodegenerative diseases such as Alzheimer’s disease, Parkinson disease, and amyotrophic lateral sclerosis, dysregulation of lipid metabolism is closely linked to synaptic dysfunction. Therefore, lipids are not only key molecules in neural regeneration and synaptic repair but may also contribute to neurodegenerative pathology when metabolic dysregulation occurs. Further research is needed to elucidate the specific mechanisms linking lipid metabolism to synaptic dysfunction and to develop targeted lipid therapies for neurological diseases.

Key words: astrocyte, central nervous system, cholesterol, glycerophospholipids, lipid, microglia, neurodegenerative diseases, sphingolipids, synapse, therapy