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Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis
Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease and a neurodegenerative disorder, affecting the upper and/or lower motor neurons. Notably, it invariably leads to death within a few years of onset. Although most ALS cases are sporadic, familial amyotrophic lateral sclero...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765192/ https://www.ncbi.nlm.nih.gov/pubmed/33333804 http://dx.doi.org/10.3390/cells9122687 |
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author | Yousefian-Jazi, Ali Seol, YunHee Kim, Jieun Ryu, Hannah L. Lee, Junghee Ryu, Hoon |
author_facet | Yousefian-Jazi, Ali Seol, YunHee Kim, Jieun Ryu, Hannah L. Lee, Junghee Ryu, Hoon |
author_sort | Yousefian-Jazi, Ali |
collection | PubMed |
description | Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease and a neurodegenerative disorder, affecting the upper and/or lower motor neurons. Notably, it invariably leads to death within a few years of onset. Although most ALS cases are sporadic, familial amyotrophic lateral sclerosis (fALS) forms 10% of the cases. In 1993, the first causative gene (SOD1) of fALS was identified. With rapid advances in genetics, over fifty potentially causative or disease-modifying genes have been found in ALS so far. Accordingly, routine diagnostic tests should encompass the oldest and most frequently mutated ALS genes as well as several new important genetic variants in ALS. Herein, we discuss current literatures on the four newly identified ALS-associated genes (CYLD, S1R, GLT8D1, and KIF5A) and the previously well-known ALS genes including SOD1, TARDBP, FUS, and C9orf72. Moreover, we review the pathogenic implications and disease mechanisms of these genes. Elucidation of the cellular and molecular functions of the mutated genes will bring substantial insights for the development of therapeutic approaches to treat ALS. |
format | Online Article Text |
id | pubmed-7765192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-77651922020-12-27 Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis Yousefian-Jazi, Ali Seol, YunHee Kim, Jieun Ryu, Hannah L. Lee, Junghee Ryu, Hoon Cells Review Amyotrophic lateral sclerosis (ALS) is the most frequent motor neuron disease and a neurodegenerative disorder, affecting the upper and/or lower motor neurons. Notably, it invariably leads to death within a few years of onset. Although most ALS cases are sporadic, familial amyotrophic lateral sclerosis (fALS) forms 10% of the cases. In 1993, the first causative gene (SOD1) of fALS was identified. With rapid advances in genetics, over fifty potentially causative or disease-modifying genes have been found in ALS so far. Accordingly, routine diagnostic tests should encompass the oldest and most frequently mutated ALS genes as well as several new important genetic variants in ALS. Herein, we discuss current literatures on the four newly identified ALS-associated genes (CYLD, S1R, GLT8D1, and KIF5A) and the previously well-known ALS genes including SOD1, TARDBP, FUS, and C9orf72. Moreover, we review the pathogenic implications and disease mechanisms of these genes. Elucidation of the cellular and molecular functions of the mutated genes will bring substantial insights for the development of therapeutic approaches to treat ALS. MDPI 2020-12-15 /pmc/articles/PMC7765192/ /pubmed/33333804 http://dx.doi.org/10.3390/cells9122687 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Yousefian-Jazi, Ali Seol, YunHee Kim, Jieun Ryu, Hannah L. Lee, Junghee Ryu, Hoon Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis |
title | Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis |
title_full | Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis |
title_fullStr | Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis |
title_full_unstemmed | Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis |
title_short | Pathogenic Genome Signatures That Damage Motor Neurons in Amyotrophic Lateral Sclerosis |
title_sort | pathogenic genome signatures that damage motor neurons in amyotrophic lateral sclerosis |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765192/ https://www.ncbi.nlm.nih.gov/pubmed/33333804 http://dx.doi.org/10.3390/cells9122687 |
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