Olfactory dysfunction is a common disorder in the general population. There are multiple causes, one of which being ciliopathies, an emerging class of human hereditary genetic disorders characterized by multiple symptoms due to defects in ciliary biogenesis, maintenance, and/or function. Mutations/deletions in a wide spectrum of ciliary genes have been identified to cause ciliopathies. Currently, besides symptomatic therapy, there is no available therapeutic treatment option for olfactory dysfunction caused by ciliopathies. Multiple studies have demonstrated that targeted gene replacement can restore the morphology and function of olfactory cilia in olfactory sensory neurons and further re-establish the odor-guided behaviors in animals. Therefore, targeted gene replacement could be potentially used to treat olfactory dysfunction in ciliopathies. However, due to the potential limitations of single-gene therapy for polygenic mutation-induced diseases, alternative therapeutic targets for broader curative measures need to be developed for olfactory dysfunction, and also for other symptoms in ciliopathies. Here we review the current understanding of ciliogenesis and maintenance of olfactory cilia. Furthermore, we emphasize signaling mechanisms that may be involved in the regulation of olfactory ciliary length and highlight potential alternative therapeutic targets for the treatment of ciliopathy-induced dysfunction in the olfactory system and even in other ciliated organ systems.

中文翻译：

---

纤毛病嗅觉功能障碍的潜在治疗靶点超越单基因替代

嗅觉功能障碍是普通人群的常见疾病。有多种原因，其中之一是纤毛病，这是一类新兴的人类遗传性遗传疾病，其特征是由于纤毛生物发生、维持和/或功能缺陷导致的多种症状。已确定多种纤毛基因的突变/缺失会导致纤毛病。目前，除对症治疗外，纤毛病引起的嗅觉功能障碍尚无可用的治疗选择。多项研究表明，靶向基因置换可以恢复嗅觉感觉神经元中嗅纤毛的形态和功能，并进一步重建动物的气味引导行为。因此，靶向基因替代可能用于治疗纤毛病的嗅觉功能障碍。然而，由于单基因治疗对多基因突变引起的疾病的潜在限制，需要为嗅觉功能障碍以及纤毛病的其他症状开发更广泛的治疗措施的替代治疗靶点。在这里，我们回顾了目前对纤毛发生和嗅纤毛维持的理解。此外，我们强调了可能涉及嗅觉纤毛长度调节的信号传导机制，并强调了治疗纤毛病引起的嗅觉系统甚至其他纤毛器官系统功能障碍的潜在替代治疗靶点。以及纤毛病的其他症状。在这里，我们回顾了目前对纤毛发生和嗅纤毛维持的理解。此外，我们强调了可能涉及嗅觉纤毛长度调节的信号传导机制，并强调了治疗纤毛病引起的嗅觉系统甚至其他纤毛器官系统功能障碍的潜在替代治疗靶点。以及纤毛病的其他症状。在这里，我们回顾了目前对纤毛发生和嗅纤毛维持的理解。此外，我们强调了可能涉及嗅觉纤毛长度调节的信号传导机制，并强调了治疗纤毛病引起的嗅觉系统甚至其他纤毛器官系统功能障碍的潜在替代治疗靶点。