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

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 a...

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Autores principales: Saito, Masaki, Otsu, Wataru, Miyadera, Keiko, Nishimura, Yuhei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538646/
https://www.ncbi.nlm.nih.gov/pubmed/37780208
http://dx.doi.org/10.3389/fmolb.2023.1232188
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author Saito, Masaki
Otsu, Wataru
Miyadera, Keiko
Nishimura, Yuhei
author_facet Saito, Masaki
Otsu, Wataru
Miyadera, Keiko
Nishimura, Yuhei
author_sort Saito, Masaki
collection PubMed
description 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.
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spelling pubmed-105386462023-09-29 Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets Saito, Masaki Otsu, Wataru Miyadera, Keiko Nishimura, Yuhei Front Mol Biosci Molecular Biosciences 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. Frontiers Media S.A. 2023-09-14 /pmc/articles/PMC10538646/ /pubmed/37780208 http://dx.doi.org/10.3389/fmolb.2023.1232188 Text en Copyright © 2023 Saito, Otsu, Miyadera and Nishimura. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Saito, Masaki
Otsu, Wataru
Miyadera, Keiko
Nishimura, Yuhei
Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets
title Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets
title_full Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets
title_fullStr Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets
title_full_unstemmed Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets
title_short Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets
title_sort recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10538646/
https://www.ncbi.nlm.nih.gov/pubmed/37780208
http://dx.doi.org/10.3389/fmolb.2023.1232188
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