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Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective degeneration of upper and lower motor neurons. Currently, there are no effective biomarkers and fundamental therapies for this disease. Dysregulation in RNA metabolism plays a critical role in the...

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Autores principales: Koike, Yuka, Onodera, Osamu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989161/
https://www.ncbi.nlm.nih.gov/pubmed/36895420
http://dx.doi.org/10.3389/fnins.2023.1131758
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author Koike, Yuka
Onodera, Osamu
author_facet Koike, Yuka
Onodera, Osamu
author_sort Koike, Yuka
collection PubMed
description Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective degeneration of upper and lower motor neurons. Currently, there are no effective biomarkers and fundamental therapies for this disease. Dysregulation in RNA metabolism plays a critical role in the pathogenesis of ALS. With the contribution of Next Generation Sequencing, the functions of non-coding RNAs (ncRNAs) have gained increasing interests. Especially, micro RNAs (miRNAs), which are tissue-specific small ncRNAs of about 18–25 nucleotides, have emerged as key regulators of gene expression to target multiple molecules and pathways in the central nervous system (CNS). Despite intensive recent research in this field, the crucial links between ALS pathogenesis and miRNAs remain unclear. Many studies have revealed that ALS-related RNA binding proteins (RBPs), such as TAR DNA-binding protein 43 (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS), regulate miRNAs processing in both the nucleus and cytoplasm. Of interest, Cu(2+)/Zn(2+) superoxide dismutase (SOD1), a non-RBP associated with familial ALS, shows partially similar properties to these RBPs via the dysregulation of miRNAs in the cellular pathway related to ALS. The identification and validation of miRNAs are important to understand the physiological gene regulation in the CNS, and the pathological implications in ALS, leading to a new avenue for early diagnosis and gene therapies. Here, we offer a recent overview regarding the mechanism underlying the functions of multiple miRNAs across TDP-43, FUS, and SOD1 with the context of cell biology, and challenging for clinical applications in ALS.
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spelling pubmed-99891612023-03-08 Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications Koike, Yuka Onodera, Osamu Front Neurosci Neuroscience Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the selective degeneration of upper and lower motor neurons. Currently, there are no effective biomarkers and fundamental therapies for this disease. Dysregulation in RNA metabolism plays a critical role in the pathogenesis of ALS. With the contribution of Next Generation Sequencing, the functions of non-coding RNAs (ncRNAs) have gained increasing interests. Especially, micro RNAs (miRNAs), which are tissue-specific small ncRNAs of about 18–25 nucleotides, have emerged as key regulators of gene expression to target multiple molecules and pathways in the central nervous system (CNS). Despite intensive recent research in this field, the crucial links between ALS pathogenesis and miRNAs remain unclear. Many studies have revealed that ALS-related RNA binding proteins (RBPs), such as TAR DNA-binding protein 43 (TDP-43) and fused in sarcoma/translocated in liposarcoma (FUS), regulate miRNAs processing in both the nucleus and cytoplasm. Of interest, Cu(2+)/Zn(2+) superoxide dismutase (SOD1), a non-RBP associated with familial ALS, shows partially similar properties to these RBPs via the dysregulation of miRNAs in the cellular pathway related to ALS. The identification and validation of miRNAs are important to understand the physiological gene regulation in the CNS, and the pathological implications in ALS, leading to a new avenue for early diagnosis and gene therapies. Here, we offer a recent overview regarding the mechanism underlying the functions of multiple miRNAs across TDP-43, FUS, and SOD1 with the context of cell biology, and challenging for clinical applications in ALS. Frontiers Media S.A. 2023-02-21 /pmc/articles/PMC9989161/ /pubmed/36895420 http://dx.doi.org/10.3389/fnins.2023.1131758 Text en Copyright © 2023 Koike and Onodera. 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 Neuroscience
Koike, Yuka
Onodera, Osamu
Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications
title Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications
title_full Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications
title_fullStr Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications
title_full_unstemmed Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications
title_short Implications of miRNAs dysregulation in amyotrophic lateral sclerosis: Challenging for clinical applications
title_sort implications of mirnas dysregulation in amyotrophic lateral sclerosis: challenging for clinical applications
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9989161/
https://www.ncbi.nlm.nih.gov/pubmed/36895420
http://dx.doi.org/10.3389/fnins.2023.1131758
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