Wang Zhiyi, Zhu Xiaofan, Huang Zhenzhou, Ren Kaidi, Ran Jie, Yang Yang
Department of Translational Medicine Center, Clinical Systems Biology Laboratories, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
Center for Cell Structure and Function, Shandong Provincial Key Laboratory of Animal Resistance Biology, College of Life Sciences, Shandong Normal University, Jinan, 250014, China.
Adv Sci (Weinh). 2025 Jun;12(21):e2412921. doi: 10.1002/advs.202412921. Epub 2025 Apr 1.
HDAC6 is integral to the regulation of primary cilia, which are specialized structures that serve as crucial signaling hubs for cellular communication and environmental response. These ciliary functions are essential for maintaining cellular homeostasis and orchestrating developmental processes. Dysregulation of HDAC6 activity is implicated in ciliopathies, a group of disorders characterized by defective ciliary structure or function, resulting in widespread organ involvement and significant morbidity. This review provides a comprehensive examination of the molecular dynamics of HDAC6 in the context of ciliogenesis and ciliopathies, emphasizing its dual role in the deacetylation of microtubules and regulation of the ciliary axoneme. Furthermore, HDAC6 interacts with key signaling molecules, modulating processes ranging from cell cycle regulation to inflammatory responses, which highlights its central role in cellular physiology and pathology. The therapeutic potential of HDAC6 inhibitors has been explored, with promising results in various disease models, including retinal and renal ciliopathies, highlighting their ability to restore normal ciliary function. This analysis not only underscores the critical importance of HDAC6 in maintaining ciliary integrity but also illustrates how targeting the HDAC6-cilia axis could provide a groundbreaking approach to treating these complex disorders. In doing so, this review sets the stage for future investigations into HDAC6-targeted therapies, potentially transforming the clinical management of ciliopathies and significantly improving patient outcomes.
HDAC6对于初级纤毛的调控至关重要，初级纤毛是一种特殊结构，作为细胞通讯和环境应答的关键信号枢纽。这些纤毛功能对于维持细胞内稳态和协调发育过程至关重要。HDAC6活性失调与纤毛病有关，纤毛病是一组以纤毛结构或功能缺陷为特征的疾病，会导致广泛的器官受累和严重发病。本综述全面探讨了HDAC6在纤毛发生和纤毛病背景下的分子动力学，强调了其在微管去乙酰化和纤毛轴丝调控中的双重作用。此外，HDAC6与关键信号分子相互作用，调节从细胞周期调控到炎症反应等多种过程，这突出了其在细胞生理学和病理学中的核心作用。HDAC6抑制剂的治疗潜力已得到探索，在包括视网膜和肾脏纤毛病在内的各种疾病模型中取得了有前景的结果，凸显了它们恢复正常纤毛功能的能力。这一分析不仅强调了HDAC6在维持纤毛完整性方面的至关重要性，还说明了靶向HDAC6 - 纤毛轴可能为治疗这些复杂疾病提供一种开创性方法。通过这样做，本综述为未来针对HDAC6的治疗研究奠定了基础，有可能改变纤毛病的临床管理并显著改善患者预后。
