听力损失相关的NOX家族蛋白研究进展

Research progress on NOX/DUOX family proteins in auditory physiology and pathogenesis

摘要:

还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶（NOX）家族蛋白通过调控活性氧（ROS）的生成参与多种基础细胞生理过程，更与多种人类疾病的发生、发展密切相关。在内耳中，ROS作为关键信号分子，参与调控内耳细胞的代谢活动、信号传导等重要生理过程。当ROS生成失衡，引发级联氧化应激反应，会导致内耳细胞结构和功能的损伤。这种氧化应激机制是多种听力损失（如噪声性耳聋、老年性聋、药物性耳聋等）的共同病理基础。作为细胞内ROS产生的主要来源之一，NOX家族蛋白通过介导氧化应激反应，在听力系统的发育或功能维持中扮演着重要角色。这一作用机制提示了NOX家族蛋白可能是防治听力损失的重要潜在靶点。该文综述了NOX家族蛋白在听觉系统中的功能和机制，以及靶向NOX家族蛋白的药物研发进展，期望对推动NOX靶向治疗、改善患者听力提供参考。

Abstract:

The NOX family proteins, as core components of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, regulate the production of reactive oxygen species (ROS) to mediate fundamental cellular physiological processes and are critically implicated in the pathogenesis of various human diseases. Within the inner ear, ROS serve as pivotal signaling molecules involved in modulating essential physiological functions such as metabolic activities and signal transduction in auditory cells. However, dysregulated ROS generation triggers cascading oxidative stress responses, leading to progressive structural and functional damage in cochlear cells. Studies demonstrate that such oxidative stress mechanisms constitute a common pathological basis for multiple forms of hearing loss, including noise-induced hearing loss, age-related hearing loss, and ototoxic drug-induced hearing loss. As primary intracellular sources of ROS, NOX family proteins play crucial roles in auditory system development and functional maintenance by mediating oxidative stress pathways. This mechanistic involvement highlights NOX family proteins as promising therapeutic targets for hearing loss intervention. This review systematically elucidates the functional roles and molecular mechanisms of NOX family proteins in the auditory system, establishing a foundation for comprehensively deciphering their pathophysiological contributions to hearing impairment. Targeting NOX family proteins holds significant potential for developing novel therapeutic agents and intervention strategies to ameliorate auditory dysfunction in clinical settings.