Serpieri Valentina, D'Abrusco Fulvio, Valente Enza Maria
Department of Molecular Medicine, University of Pavia, Pavia, Italy.
Neurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy.
Lancet Neurol. 2025 Sep;24(9):763-775. doi: 10.1016/S1474-4422(25)00226-1. Epub 2025 Jul 21.
Primary cilia are ubiquitous organelles, which play essential roles in sensing and transducing cellular signals and in mediating key developmental pathways. Pathogenic variants in genes encoding for ciliary proteins give rise to a spectrum of disorders termed primary ciliopathies. The archetypal neurodevelopmental ciliopathy is Joubert syndrome. However, in the past decade, primary cilia have been implicated in several other neurological disorders, including neurodevelopmental disorders, malformations of cortical development, neurodegenerative disorders, and psychiatric disorders. Therapeutic approaches for cilia-related disorders are still scarce. Strategies based on gene therapy and antisense oligonucleotides show promising results, especially for the treatment of retinal ciliopathies, and are currently moving towards clinical translation. Other approaches based on drug repurposing or the use of small molecules, despite positive results in a variety of cellular and animal models, are still in the experimental stage.
原发性纤毛是普遍存在的细胞器，在感知和转导细胞信号以及介导关键发育途径中发挥着重要作用。编码纤毛蛋白的基因中的致病变异会引发一系列称为原发性纤毛病的疾病。典型的神经发育性纤毛病是Joubert综合征。然而，在过去十年中，原发性纤毛与其他几种神经系统疾病有关，包括神经发育障碍、皮质发育畸形、神经退行性疾病和精神疾病。针对纤毛相关疾病的治疗方法仍然很少。基于基因治疗和反义寡核苷酸的策略显示出有前景的结果，特别是对于视网膜纤毛病的治疗，目前正朝着临床转化发展。尽管在各种细胞和动物模型中取得了积极成果，但基于药物重新利用或小分子使用的其他方法仍处于实验阶段。
