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Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD

TAR DNA binding protein 43 (TDP-43) is a DNA/RNA binding protein involved in pivotal cellular functions, especially in RNA metabolism. Hyperphosphorylated and ubiquitinated TDP-43-positive neuronal cytoplasmic inclusions are identified in the brain and spinal cord in most cases of amyotrophic latera...

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Autores principales: Tamaki, Yoshitaka, Urushitani, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604209/
https://www.ncbi.nlm.nih.gov/pubmed/36293362
http://dx.doi.org/10.3390/ijms232012508
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author Tamaki, Yoshitaka
Urushitani, Makoto
author_facet Tamaki, Yoshitaka
Urushitani, Makoto
author_sort Tamaki, Yoshitaka
collection PubMed
description TAR DNA binding protein 43 (TDP-43) is a DNA/RNA binding protein involved in pivotal cellular functions, especially in RNA metabolism. Hyperphosphorylated and ubiquitinated TDP-43-positive neuronal cytoplasmic inclusions are identified in the brain and spinal cord in most cases of amyotrophic lateral sclerosis (ALS) and a substantial proportion of frontotemporal lobar degeneration (FTLD) cases. TDP-43 dysfunctions and cytoplasmic aggregation seem to be the central pathogenicity in ALS and FTLD. Therefore, unraveling both the physiological and pathological mechanisms of TDP-43 may enable the exploration of novel therapeutic strategies. This review highlights the current understanding of TDP-43 biology and pathology, describing the cellular processes involved in the pathogeneses of ALS and FTLD, such as post-translational modifications, RNA metabolism, liquid–liquid phase separation, proteolysis, and the potential prion-like propagation propensity of the TDP-43 inclusions.
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spelling pubmed-96042092022-10-27 Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD Tamaki, Yoshitaka Urushitani, Makoto Int J Mol Sci Review TAR DNA binding protein 43 (TDP-43) is a DNA/RNA binding protein involved in pivotal cellular functions, especially in RNA metabolism. Hyperphosphorylated and ubiquitinated TDP-43-positive neuronal cytoplasmic inclusions are identified in the brain and spinal cord in most cases of amyotrophic lateral sclerosis (ALS) and a substantial proportion of frontotemporal lobar degeneration (FTLD) cases. TDP-43 dysfunctions and cytoplasmic aggregation seem to be the central pathogenicity in ALS and FTLD. Therefore, unraveling both the physiological and pathological mechanisms of TDP-43 may enable the exploration of novel therapeutic strategies. This review highlights the current understanding of TDP-43 biology and pathology, describing the cellular processes involved in the pathogeneses of ALS and FTLD, such as post-translational modifications, RNA metabolism, liquid–liquid phase separation, proteolysis, and the potential prion-like propagation propensity of the TDP-43 inclusions. MDPI 2022-10-19 /pmc/articles/PMC9604209/ /pubmed/36293362 http://dx.doi.org/10.3390/ijms232012508 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Tamaki, Yoshitaka
Urushitani, Makoto
Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD
title Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD
title_full Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD
title_fullStr Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD
title_full_unstemmed Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD
title_short Molecular Dissection of TDP-43 as a Leading Cause of ALS/FTLD
title_sort molecular dissection of tdp-43 as a leading cause of als/ftld
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9604209/
https://www.ncbi.nlm.nih.gov/pubmed/36293362
http://dx.doi.org/10.3390/ijms232012508
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