[1]张倩,王川,吴玉梅.肝X受体与中枢神经系统疾病：从机制探索到临床应用[J].陕西医学杂志,2025,54(10):1436-封3.[doi:DOI:10.3969/j.issn.1000-7377.2025.10.027]
　ZHANG Qian,WANG Chuan,WU Yumei.Liver X receptor and central nervous system diseases：From mechanistic exploration to clinical application[J].,2025,54(10):1436-封3.[doi:DOI:10.3969/j.issn.1000-7377.2025.10.027]
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肝X受体与中枢神经系统疾病：从机制探索到临床应用

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年10期
页码:
1436-封3
栏目:
综 述
出版日期:
2025-10-05

文章信息/Info

Title:
Liver X receptor and central nervous system diseases：From mechanistic exploration to clinical application
作者:
张倩1; 2; 王川1; 吴玉梅2
（1.陕西中医药大学药学院，陕西 咸阳 712046；2.空军军医大学药理学教研室，陕西 西安 710032）
Author(s):
ZHANG Qian1; 2; WANG Chuan1; WU Yumei2
(1.Department of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046,China;2.Department of Pharmacology,School of Pharmacy,Air Force Medical University,Xi’an 710032,China)
关键词:
肝X受体; 中枢神经系统; 胆固醇代谢稳态; 神经炎症反应; 神经发生; 胶质细胞功能
Keywords:
Liver X receptors; Central nervous system; Cholesterol metabolic homeostasis; Neuroinflammatory response; Neurogenesis; Glial cell function
分类号:
R 741
DOI:
DOI:10.3969/j.issn.1000-7377.2025.10.027
文献标志码:
A
摘要:
肝X受体（LXR）是核受体超家族的重要成员，在中枢神经系统（CNS）疾病的病理生理中发挥重要作用。LXR通过调节胆固醇代谢稳态、抑制神经炎症和促进神经发生等机制，展现出显著的神经保护作用，因而成为治疗CNS疾病的潜在靶点。然而，传统LXR激动剂在临床转化中面临肝脂肪变性和高脂血症等代谢性副作用的显著挑战，严重限制了其临床应用。本综述系统阐述了LXR的信号转导机制及其在CNS中的生理与病理作用，并针对传统LXR激动剂的代谢副作用，提出了多种优化策略，包括开发选择性更高的新型LXR激动剂；优化靶向递送技术以提高药物在CNS的特异性分布；以及探索天然LXR激动剂等。这些策略旨在提升LXR激动剂的疗效，降低代谢副作用，为LXR在CNS疾病治疗的未来研究和临床应用提供新的思路和理论支持。
Abstract:
Liver X receptor (LXR) is a key member of the nuclear receptor superfamily and plays a significant role in the pathophysiology of central nervous system (CNS) diseases.By regulating cholesterol metabolic homeostasis,suppressing neuroinflammation,and promoting neurogenesis,LXR exhibits significant neuroprotective effects,making it a promising therapeutic target for CNS disorders.However,the clinical translation of traditional LXR agonists faces major challenges,particularly due to metabolic side effects such as hepatic steatosis and hyperlipidemia,which severely limit their clinical applicability.This review systematically outlines the signal transduction mechanisms of LXR and its physiological and pathological roles in the CNS.To address the metabolic side effects of conventional LXR agonists,multiple optimization strategies are proposed,including the development of novel,more selective LXR agonists,the improvement of targeted delivery technologies to enhance CNS-specific distribution,and the exploration of natural LXR agonists.These approaches aim to enhance the therapeutic efficacy of LXR agonists while minimizing metabolic adverse effects,thereby providing new insights and theoretical support for future research and clinical applications of LXR in treating CNS diseases.

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备注/Memo

备注/Memo:
国家自然科学基金资助项目（82071515）
更新日期/Last Update: 2025-10-09