Tao Kefan, Zong Yanjun, Liu Xiaozhou, Shi Xinyu, Zhao Zhengdong, Sun Yu
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Institute of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Neurosci Bull. 2025 Jul 9. doi: 10.1007/s12264-025-01446-9.
Hearing loss is one of the most prevalent sensory disorders affecting the human nervous system. Liquid-liquid phase separation (LLPS) is a physiological process that facilitates the reversible and dynamic assembly of biomolecular condensates. Increasing evidence suggests that LLPS plays a significant role in the pathogenesis of hereditary hearing loss. Nevertheless, there is a conspicuous lack of systematic investigations exploring the impact of LLPS abnormalities on the etiology of hereditary hearing loss. In this review, we examine the mechanisms by which dysfunctions in LLPS contribute to hereditary hearing loss, specifically focusing on its effects on mechanoelectrical transduction in hair bundles, transcriptional regulation, post-transcriptional modifications, the actin cytoskeleton, ion homeostasis within the inner ear, and energy and redox homeostasis. Furthermore, we evaluate the considerable potential of targeting LLPS as a therapeutic approach for hearing loss and propose innovative perspectives on LLPS that may guide future research initiatives in the field of auditory disorders.
听力损失是影响人类神经系统的最常见感觉障碍之一。液-液相分离（LLPS）是一种促进生物分子凝聚物可逆和动态组装的生理过程。越来越多的证据表明，LLPS在遗传性听力损失的发病机制中起重要作用。然而，明显缺乏系统研究来探索LLPS异常对遗传性听力损失病因的影响。在本综述中，我们研究了LLPS功能障碍导致遗传性听力损失的机制，特别关注其对毛束机械电转导、转录调控、转录后修饰、肌动蛋白细胞骨架、内耳离子稳态以及能量和氧化还原稳态的影响。此外，我们评估了将LLPS作为听力损失治疗方法的巨大潜力，并提出了关于LLPS的创新观点，这些观点可能会指导听觉障碍领域未来的研究工作。
