以小分子治疗策略更聚焦于听力损失：一篇综述。

文献信息

中文摘要

背景与目的： 听力损失（HL）是全球最常见的感觉障碍之一，对生活质量和日常功能有重大影响。尽管人工耳蜗和助听器显著改善了听力障碍的管理，但这些设备并未直接解决HL的潜在致病机制。本综述旨在总结HL的病理生理学和分类，并讨论小分子（SMs）在其管理中的潜在治疗应用。
方法： 本综述聚焦于不同形式HL涉及的主要病理机制，并总结基于SM的临床前和临床相关治疗策略。所综述的策略包括药理学伴侣、转录调节、离子通道调节剂、神经保护化合物、凋亡抑制剂和再生方法。
结果： SMs具有使其适合靶向HL相关特定分子通路的理化性质。当前证据表明，基于SM的干预可能通过多种机制发挥作用，包括减轻氧化应激、炎症和凋亡；调节离子通道；支持听觉神经元存活和功能；以及促进再生信号传导。
结论： 基于SM的治疗方法代表了解决HL潜在分子和细胞机制的有前景的策略。这些方法可能为未来研究提供有价值的方向，并支持为听力障碍个体开发靶向疗法。

英文摘要

BACKGROUND AND AIMS: Hearing loss (HL) is one of the most common sensory impairments worldwide and has substantial effects on quality of life and daily functioning. Although cochlear implants and hearing aids have markedly improved the management of hearing impairment, these devices do not directly address the underlying pathogenic mechanisms of HL. This review aims to summarize the pathophysiology and classification of HL and to discuss the potential therapeutic applications of small molecules (SMs) in its management.
METHODS: This review focuses on the major pathological mechanisms involved in different forms of HL and summarizes preclinical and clinically relevant SM-based therapeutic approaches. The reviewed strategies include pharmacological chaperones, transcriptional modulation, ion-channel modulators, neuroprotective compounds, apoptosis inhibitors, and regenerative approaches.
RESULTS: SMs possess physicochemical properties that make them suitable for targeting specific molecular pathways involved in HL. Current evidence suggests that SM-based interventions may act through diverse mechanisms, including attenuation of oxidative stress, inflammation, and apoptosis; modulation of ion channels; support of auditory neuron survival and function; and promotion of regenerative signaling.
CONCLUSION: SM-based therapeutic approaches represent promising strategies for addressing the molecular and cellular mechanisms underlying HL. These approaches may provide valuable directions for future research and support the development of targeted therapies for individuals with hearing impairment.