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C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies

Hexanucleotide expansion in C9orf72 has been related to several phenotypes to date, complicating the clinical recognition of these neurodegenerative disorders. An early diagnosis can improve the management of patients, promoting early administration of therapeutic supportive strategies. Here, we rep...

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Autores principales: Zampatti, Stefania, Peconi, Cristina, Campopiano, Rosa, Gambardella, Stefano, Caltagirone, Carlo, Giardina, Emiliano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226392/
https://www.ncbi.nlm.nih.gov/pubmed/35754952
http://dx.doi.org/10.3389/fnagi.2022.907122
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author Zampatti, Stefania
Peconi, Cristina
Campopiano, Rosa
Gambardella, Stefano
Caltagirone, Carlo
Giardina, Emiliano
author_facet Zampatti, Stefania
Peconi, Cristina
Campopiano, Rosa
Gambardella, Stefano
Caltagirone, Carlo
Giardina, Emiliano
author_sort Zampatti, Stefania
collection PubMed
description Hexanucleotide expansion in C9orf72 has been related to several phenotypes to date, complicating the clinical recognition of these neurodegenerative disorders. An early diagnosis can improve the management of patients, promoting early administration of therapeutic supportive strategies. Here, we report known clinical presentations of C9orf72-related neurodegenerative disorders, pointing out suggestive phenotypes that can benefit the genetic characterization of patients. Considering the high variability of C9orf72-related disorder, frequent and rare manifestations are described, with detailed clinical, instrumental evaluation, and supportive therapeutical approaches. Furthermore, to improve the understanding of molecular pathways of the disease and potential therapeutical targets, a detailed description of the cellular mechanisms related to the pathological effect of C9orf72 is reported. New promising therapeutical strategies and ongoing studies are reported highlighting their molecular role in cellular pathological pathways of C9orf72. These therapeutic approaches are particularly promising because they seem to stop the disease before neuronal damage. The knowledge of clinical and molecular features of C9orf72-related neurodegenerative disorders improves the therapeutical application of known strategies and will lay the basis for the development of new potential therapies.
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spelling pubmed-92263922022-06-25 C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies Zampatti, Stefania Peconi, Cristina Campopiano, Rosa Gambardella, Stefano Caltagirone, Carlo Giardina, Emiliano Front Aging Neurosci Aging Neuroscience Hexanucleotide expansion in C9orf72 has been related to several phenotypes to date, complicating the clinical recognition of these neurodegenerative disorders. An early diagnosis can improve the management of patients, promoting early administration of therapeutic supportive strategies. Here, we report known clinical presentations of C9orf72-related neurodegenerative disorders, pointing out suggestive phenotypes that can benefit the genetic characterization of patients. Considering the high variability of C9orf72-related disorder, frequent and rare manifestations are described, with detailed clinical, instrumental evaluation, and supportive therapeutical approaches. Furthermore, to improve the understanding of molecular pathways of the disease and potential therapeutical targets, a detailed description of the cellular mechanisms related to the pathological effect of C9orf72 is reported. New promising therapeutical strategies and ongoing studies are reported highlighting their molecular role in cellular pathological pathways of C9orf72. These therapeutic approaches are particularly promising because they seem to stop the disease before neuronal damage. The knowledge of clinical and molecular features of C9orf72-related neurodegenerative disorders improves the therapeutical application of known strategies and will lay the basis for the development of new potential therapies. Frontiers Media S.A. 2022-06-10 /pmc/articles/PMC9226392/ /pubmed/35754952 http://dx.doi.org/10.3389/fnagi.2022.907122 Text en Copyright © 2022 Zampatti, Peconi, Campopiano, Gambardella, Caltagirone and Giardina. 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 Aging Neuroscience
Zampatti, Stefania
Peconi, Cristina
Campopiano, Rosa
Gambardella, Stefano
Caltagirone, Carlo
Giardina, Emiliano
C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies
title C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies
title_full C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies
title_fullStr C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies
title_full_unstemmed C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies
title_short C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies
title_sort c9orf72-related neurodegenerative diseases: from clinical diagnosis to therapeutic strategies
topic Aging Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9226392/
https://www.ncbi.nlm.nih.gov/pubmed/35754952
http://dx.doi.org/10.3389/fnagi.2022.907122
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