The relevance of primary cilia in neurological disorders

Abstract

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.