纤毛生成与自噬的分子机制探究及疾病治疗前景  

Molecular mechanisms and prospects for disease treatment of ciliogenesis and autophagy

作　　者：胡昊良 汪锦 刘佳妍 黄仕芳 李玉婷[3] 陈哲 陈临溪 HU Hao-liang;WANG Jin;LIU Jia-yan;HUANG Shi-fang;LI Yu-ting;CHEN Zhe;CHEN Lin-xi(Changde Research Centre for Artificial Intelligence and Biomedicine,Hunan University of Arts and Science,Changde Hunan 415000,China;Institute of Pharmacy and Pharmacology,College of Basic Medical Science,Hengyang Medical School,University of South China,Hengyang Hunan 421200,China;Dept of Pharmacology,Yongzhou Vocational Technical College,Yongzhou Hunan 425000,China)

机构地区：[1]湖南文理学院,常德市人工智能与生物医学研究中心,湖南常德415000 [2]南华大学,衡阳医学院,药学院药理学教研室,湖南衡阳421000 [3]永州职业技术学院药学系,湖南永州425000

出　　处：《中国药理学通报》2025年第4期631-637,共7页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No.82304495);湖南省自然科学基金资助项目(No.2024JJ4031,2024JJ5346,2022JJ40291,2023JJ60248);中国博士后基金-面上项目(No.2023M741607);湖南省教育厅-重点项目(No.23A0505);常德市技术研发和创新引导项目(No.2023ZD03)。

摘　　要：初级纤毛是细胞中的一种感受性细胞器,在其生成和运输过程中参与调控细胞自噬、分解代谢等生物学过程。自噬则是一种细胞自我保护的机制,通过清除受损细胞器、蛋白质聚集和病毒来维持细胞内稳态。结合近期研究报道,本综述全面阐述了初级纤毛与自噬之间存在的复杂双向串扰,即纤毛依赖的信号通路对于激活细胞自噬至关重要,自噬能够通过降解特定纤毛蛋白来调节纤毛的生成和长度。此外,初级纤毛和自噬的失调参与到多囊肾病、结节性硬化症等多种纤毛相关性疾病的临床表现和发病机制。在药物治疗方面,该文对靶向纤毛生成的小分子抑制剂进行了全面总结,如细胞骨架药物、Hedgehog信号通路抑制剂等。尽管该类药物目前在临床使用中尚存在一定的局限性,但对于开发高度特异性的靶向纤毛生成小分子抑制剂、以及纤毛病和相关癌症的治疗指明了方向。综上,该文通过系统性探讨了纤毛生成、自噬、及其关联疾病和治疗药物,为未来深入阐明纤毛生成与自噬的互作网络、探索其在疾病发展中的病理机制和治疗策略提供了新思路。Cilia,as cellular sensory organelles,actively participate in and regulate cellular processes such as autophagy and metabolic breakdown during their generation and transportation.Autophagy,on the other hand,is a cell self-protection mechanism that maintains cellular homeostasis by clearing aggregates and damaged organelles.Combining recent research findings,this review comprehensively elucidates the bidirectional crosstalk between primary cilia and autophagy.Specifically,it highlights the crucial role of cilia-dependent signaling pathways in activating cellular autophagy and how autophagy regulates cilia generation and length by degrading specific ciliary proteins.Moreover,the dysregulation of primary cilia and autophagy is closely associated with the clinical manifestations and pathogenesis of various ciliopathy-related diseases such as polycystic kidney disease and tuberous sclerosis.In terms of pharmacotherapy,this review provides a comprehensive and in-depth overview of small molecule inhibitors targeting ciliogenesis,including cytoskeletal drugs and Hedgehog signaling pathway inhibitors.Despite the current limitations in clinical use,these drugs lay the groundwork for developing highly specific targeted small molecule inhibitors of ciliogenesis and for the treatment of ciliopathies and cancers.By systematically discussing ciliogenesis,autophagy,diseases and drugs,this review offers new insights for further elucidating the crosstalk between ciliogenesis and autophagy,exploring their pathological mechanisms in disease development,and developing therapeutic strategies in the future.

关 键 词：纤毛 自噬 纤毛形成 纤毛相关疾病 小分子抑制剂 选择性自噬 

分 类 号：R329.24[医药卫生—人体解剖和组织胚胎学] R392[医药卫生—基础医学] R692.12R742.89R916.4