PPAR-γ调控脑胆固醇代谢清除β-淀粉样蛋白改善阿尔茨海默病的研究进展  

Research progress of PPAR-γregulating brain cholesterol metabolism to clearβ-amyloid protein to improve Alzheimer’s disease

作　　者：段学庆 王少锋 陈先玉 郝彦伟 李佳欣 李莉[1] 徐世军[2] 李斌[1] DUAN Xue-qing;WANG Shao-feng;CHEN Xian-yu;HAO Yan-wei;LI Jia-xin;LI Li;XU Shi-jun;LI Bin(Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610075;School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China)

机构地区：[1]成都中医药大学附属医院,四川成都610075 [2]成都中医药大学药学院,四川成都611137

出　　处：《中国药理学通报》2024年第11期2005-2009,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 82174345,82474455)。

摘　　要：过氧化物酶体增殖物激活受体γ(peroxisome proliferators-activated receptor gamma,PPAR-γ)是配体激活的核转录因子超家族成员之一。活化的PPAR-γ参与调节许多中枢神经系统(central nervous system,CNS)事件,通过诱导或抑制一系列基因、蛋白等途径参与脑胆固醇代谢,从而抑制β-淀粉样蛋白(β-amyloid protein,Aβ)沉积,在阿尔茨海默病(Alzheimer’s disease,AD)中发挥着重要的神经保护作用,改善AD的记忆和认知能力,是AD的一个有潜力的靶点。旨在恢复脑胆固醇稳态的药物开发可能是抵消AD的潜在策略。该文通过分析PPAR-γ的分布、结构,聚焦PPAR-γ介导的脑胆固醇代谢与AD的生物学相关性,阐述了PPAR-γ对关键蛋白、基因及其相应分子的机制调控,为AD的治疗提供了新的参考。Peroxisome proliferator-activated receptor gamma(PPAR-γ)is a member of the ligand-activated nuclear transcription factor superfamily.Activated PPAR-γis involved in the regulation of many central nervous system(CNS)events,and is involved in cholesterol metabolism by inducing or inhibiting a series of gene pathways,thereby inhibiting the deposition ofβ-amyloid protein(Aβ).It plays an important neuroprotective role in Alzheimer’s disease(AD),improves memory and cognition in AD,and is a potential target for AD.Drug development aimed at restoring cholesterol homeostasis may be a potential strategy to counteract AD.By analyzing the distribution and structure of PPAR-γ,focusing on the biological correlation between PPAR-γ-mediated cholesterol metabolism and AD,this paper describes the mechanism regulation of PPAR-γon key proteins,genes and their corresponding molecules,providing a new reference for the treatment of AD.

关 键 词：PPAR-Γ 阿尔茨海默病 胆固醇 Β-淀粉样蛋白 天然化合物 中草药 

分 类 号：R749.16[医药卫生—神经病学与精神病学]