Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Yousefian-Jazi, Ali, Seol, YunHee, Kim, Jieun, Ryu, Hannah L., Lee, Junghee, Ryu, Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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
_version_ 1783628434124046336
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
work_keys_str_mv AT yousefianjaziali pathogenicgenomesignaturesthatdamagemotorneuronsinamyotrophiclateralsclerosis
AT seolyunhee pathogenicgenomesignaturesthatdamagemotorneuronsinamyotrophiclateralsclerosis
AT kimjieun pathogenicgenomesignaturesthatdamagemotorneuronsinamyotrophiclateralsclerosis
AT ryuhannahl pathogenicgenomesignaturesthatdamagemotorneuronsinamyotrophiclateralsclerosis
AT leejunghee pathogenicgenomesignaturesthatdamagemotorneuronsinamyotrophiclateralsclerosis
AT ryuhoon pathogenicgenomesignaturesthatdamagemotorneuronsinamyotrophiclateralsclerosis