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Pathogenesis of FUS-associated ALS and FTD: insights from rodent models

Disruptions to genes linked to RNA processing and homeostasis are implicated in the pathogenesis of two pathologically related but clinically heterogeneous neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in the Fused-in-Sarcoma (FUS) gene...

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Autores principales: Nolan, Matthew, Talbot, Kevin, Ansorge, Olaf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011941/
https://www.ncbi.nlm.nih.gov/pubmed/27600654
http://dx.doi.org/10.1186/s40478-016-0358-8
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author Nolan, Matthew
Talbot, Kevin
Ansorge, Olaf
author_facet Nolan, Matthew
Talbot, Kevin
Ansorge, Olaf
author_sort Nolan, Matthew
collection PubMed
description Disruptions to genes linked to RNA processing and homeostasis are implicated in the pathogenesis of two pathologically related but clinically heterogeneous neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in the Fused-in-Sarcoma (FUS) gene encoding a 526 amino-acid RNA-binding protein are found in a small subset of ALS cases, but FUS mutations do not appear to be a direct cause of FTD. Structural and functional similarities between FUS and another ALS-related RNA-binding protein, TDP-43, highlight the potential importance of aberrant RNA processing in ALS/FTD, and this pathway is now a major focus of interest. Recently, several research groups have reported transgenic vertebrate models of FUSopathy, with varying results. Here, we discuss the evidence for FUS pathogenicity in ALS/FTD, review the experimental approaches used and phenotypic features of FUS rodent models reported to date, and outline their contribution to our understanding of pathogenic mechanisms. Further refinement of vertebrate models will likely aid our understanding of the role of FUS in both diseases.
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spelling pubmed-50119412016-09-07 Pathogenesis of FUS-associated ALS and FTD: insights from rodent models Nolan, Matthew Talbot, Kevin Ansorge, Olaf Acta Neuropathol Commun Review Disruptions to genes linked to RNA processing and homeostasis are implicated in the pathogenesis of two pathologically related but clinically heterogeneous neurodegenerative diseases, amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Mutations in the Fused-in-Sarcoma (FUS) gene encoding a 526 amino-acid RNA-binding protein are found in a small subset of ALS cases, but FUS mutations do not appear to be a direct cause of FTD. Structural and functional similarities between FUS and another ALS-related RNA-binding protein, TDP-43, highlight the potential importance of aberrant RNA processing in ALS/FTD, and this pathway is now a major focus of interest. Recently, several research groups have reported transgenic vertebrate models of FUSopathy, with varying results. Here, we discuss the evidence for FUS pathogenicity in ALS/FTD, review the experimental approaches used and phenotypic features of FUS rodent models reported to date, and outline their contribution to our understanding of pathogenic mechanisms. Further refinement of vertebrate models will likely aid our understanding of the role of FUS in both diseases. BioMed Central 2016-09-06 /pmc/articles/PMC5011941/ /pubmed/27600654 http://dx.doi.org/10.1186/s40478-016-0358-8 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Review
Nolan, Matthew
Talbot, Kevin
Ansorge, Olaf
Pathogenesis of FUS-associated ALS and FTD: insights from rodent models
title Pathogenesis of FUS-associated ALS and FTD: insights from rodent models
title_full Pathogenesis of FUS-associated ALS and FTD: insights from rodent models
title_fullStr Pathogenesis of FUS-associated ALS and FTD: insights from rodent models
title_full_unstemmed Pathogenesis of FUS-associated ALS and FTD: insights from rodent models
title_short Pathogenesis of FUS-associated ALS and FTD: insights from rodent models
title_sort pathogenesis of fus-associated als and ftd: insights from rodent models
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5011941/
https://www.ncbi.nlm.nih.gov/pubmed/27600654
http://dx.doi.org/10.1186/s40478-016-0358-8
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