Department of Otorhinolaryngology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Otorhinolaryngology, Renhe Hospital, Baoshan District, Shanghai, China.
Biochem Pharmacol. 2024 Apr;222:116115. doi: 10.1016/j.bcp.2024.116115. Epub 2024 Mar 7.
In recent years, extensive research has been conducted on the pathogenesis of sensorineural hearing loss (SNHL). Apoptosis and necrosis have been identified to play important roles in hearing loss, but they cannot account for all hearing loss. Autophagy, a cellular process responsible for cell self-degradation and reutilization, has emerged as a significant factor contributing to hearing loss, particularly in cases of autophagy deficiency. Autophagy plays a crucial role in maintaining cell health by exerting cytoprotective and metabolically homeostatic effects in organisms. Consequently, modulating autophagy levels can profoundly impact the survival, death, and regeneration of cells in the inner ear, including hair cells (HCs) and spiral ganglion neurons (SGNs). Abnormal mitochondrial autophagy has been demonstrated in animal models of SNHL. These findings indicate the profound significance of comprehending autophagy while suggesting that our perspective on this cellular process holds promise for advancing the treatment of SNHL. Thus, this review aims to clarify the pathogenic mechanisms of SNHL and the role of autophagy in the developmental processes of various cochlear structures, including the greater epithelial ridge (GER), SGNs, and the ribbon synapse. The pathogenic mechanisms of age-related hearing loss (ARHL), also known as presbycusis, and the latest research on autophagy are also discussed. Furthermore, we underscore recent findings on the modulation of autophagy in SNHL induced by ototoxic drugs. Additionally, we suggest further research that might illuminate the complete potential of autophagy in addressing SNHL, ultimately leading to the formulation of pioneering therapeutic strategies and approaches for the treatment of deafness.
近年来，人们对感音神经性听力损失（SNHL）的发病机制进行了广泛的研究。凋亡和坏死被认为在听力损失中起重要作用，但它们不能解释所有的听力损失。自噬，一种负责细胞自我降解和再利用的细胞过程，已成为导致听力损失的一个重要因素，特别是在自噬缺陷的情况下。自噬通过在生物体中发挥细胞保护和代谢稳态作用，对维持细胞健康起着至关重要的作用。因此，调节自噬水平可以深刻影响内耳中细胞的存活、死亡和再生，包括毛细胞（HCs）和螺旋神经节神经元（SGNs）。在 SNHL 的动物模型中已经证明了异常的线粒体自噬。这些发现表明，在理解自噬的同时，我们对这个细胞过程的看法为治疗 SNHL 提供了希望，这一点非常重要。因此，本综述旨在阐明 SNHL 的发病机制以及自噬在各种耳蜗结构发育过程中的作用，包括上皮嵴（GER）、SGNs 和带状突触。还讨论了年龄相关性听力损失（ARHL）（也称为老年性聋）的发病机制以及自噬的最新研究。此外，我们强调了最近关于耳毒性药物引起的 SNHL 中自噬调节的发现。此外，我们建议进行进一步的研究，以充分发挥自噬在解决 SNHL 方面的潜力，最终为耳聋的治疗制定开创性的治疗策略和方法。
