中药和天然产物精准调控自噬的策略及其在神经退行性疾病模型中的应用  

Strategies for precise regulation of autophagy by traditional Chinese medicine and natural products and their application in neurodegenerative disease models

作　　者：董雨 路嘉宏 DONG Yu;LU Jia-Hong(State Key Laboratory of Quality Research in Chinese Medicine(University of Macao),Institute of Chinese Medical Sciences,University of Macao,Macao SAR 999078,China)

机构地区：[1]澳门大学,中药质量研究国家重点实验室(澳门大学),中华医药研究院,中国澳门999078

出　　处：《中国科学:生命科学》2025年第4期618-646,共29页Scientia Sinica(Vitae)

基　　金：澳门科技发展基金(批准号:0025/2022/A1,005/2023/SKL);澳门大学基金(批准号:MYRG2022-00094-ICMS;MYRG-GRG2023-00089-ICMSUMDF);国家自然科学基金(批准号:82271455);广东省基础与应用基础研究基金(批准号:2022A1515012416)资助。

摘　　要：自噬是真核细胞中高度保守且精细的自我更新与降解机制,对维持神经稳态至关重要.随着年龄增长,自噬功能可能出现失调,具体表现为逐渐丧失清除受损细胞器和异常蛋白质的能力.细胞内部废物的积累可能导致一系列问题,包括细胞骨架破坏、轴突运输障碍、线粒体损伤,进一步诱导神经炎症、氧化应激及突触功能异常.这些情况最终导致神经退化,促进神经退行性疾病的进展.中药和天然产物小分子在调节自噬活性和治疗神经退行性疾病方面展现出显著的潜力.然而,这些天然小分子的作用靶点不明确以及针对特定自噬相关调控通路的筛选方法局限性,制约了其作为自噬调节剂的深入研究和临床应用.本研究依据药理学文献,系统地归纳和剖析了典型药物调节自噬的关键靶点和分子机制,旨在为研发具有高特异性和显著疗效的中药和天然产物自噬调节剂提供关键的参考信息和理论支持,进而为神经退行性疾病的治疗提供更有效的策略.Autophagy is an evolutionarily conserved and highly sophisticated self-renewal and self-cleaning mechanism in eukaryotic cells required for neural homeostasis.However,the function of autophagy becomes imbalanced with age.Specifically,autophagy gradually loses the ability to clear damaged organelles or abnormal proteins.Accumulation of intracellular wastes results in problems such as cytoskeletal disruption,axonal transport defects,mitochondrial damage,and eventually,neuroinflammation,oxidative stress,and synaptic dysfunction.These events are followed by neurodegeneration and contribute to neurodegenerative diseases.Traditional Chinese Medicine(TCM)and natural products show promise as a therapy for autophagy activity and alleviating neurodegenerative diseases.However,the unclear targets and the limitations of screening techniques that target a specific autophagy-related regulatory pathway have hindered the in-depth research and clinical application of TCM and natural products as autophagy modulators.This study systematically summarizes and analyzes the key targets and molecular mechanisms of typical drugs that regulate autophagy based on pharmacological studies and aims to provide important reference data and a theoretical basis for the development of TCMderived natural autophagy modulators with high specificity and significant efficacy,offering more effective strategies for the treatment of neurodegenerative diseases.

关 键 词：中药 药物靶点 自噬 神经退行性疾病 衰老 

分 类 号：R285[医药卫生—中药学]