Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets

Frontiers in Molecular Biosciences

Molecular Biosciences

Wataru Otsu¹  Keiko Miyadera²  Yuhei Nishimura³  Masaki Saito⁴ 

[1] Department of Biomedical Research Laboratory, Gifu Pharmaceutical University, Gifu, Japan;Department of Clinical Sciences and Advanced Medicine, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, United States;Department of Integrative Pharmacology, Mie University Graduate School of Medicine, Tsu, Mie, Japan;Mie University Research Center for Cilia and Diseases, Tsu, Mie, Japan;Department of Molecular Physiology and Pathology, School of Pharma-Sciences, Teikyo University, Tokyo, Japan;

关键词: ciliary receptors;    ciliogenesis;    ciliary transport;    ciliopathy;    inherited retinal dystrophies;    photoreceptor;   

DOI  :  10.3389/fmolb.2023.1232188

 received in 2023-05-31, accepted in 2023-08-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

The primary cilium is a single immotile microtubule-based organelle that protrudes into the extracellular space. Malformations and dysfunctions of the cilia have been associated with various forms of syndromic and non-syndromic diseases, termed ciliopathies. The primary cilium is therefore gaining attention due to its potential as a therapeutic target. In this review, we examine ciliary receptors, ciliogenesis, and ciliary trafficking as possible therapeutic targets. We first discuss the mechanisms of selective distribution, signal transduction, and physiological roles of ciliary receptors. Next, pathways that regulate ciliogenesis, specifically the Aurora A kinase, mammalian target of rapamycin, and ubiquitin-proteasome pathways are examined as therapeutic targets to regulate ciliogenesis. Then, in the photoreceptors, the mechanism of ciliary trafficking which takes place at the transition zone involving the ciliary membrane proteins is reviewed. Finally, some of the current therapeutic advancements highlighting the role of large animal models of photoreceptor ciliopathy are discussed.

【 授权许可】

Unknown   
Copyright © 2023 Saito, Otsu, Miyadera and Nishimura.