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Local Translation in Nervous System Pathologies

Dendrites and axons can extend dozens to hundreds of centimeters away from the cell body so that a single neuron can sense and respond to thousands of stimuli. Thus, for an accurate function of dendrites and axons the neuronal proteome needs to be asymmetrically distributed within neurons. Protein a...

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Autores principales: Gamarra, María, de la Cruz, Aida, Blanco-Urrejola, Maite, Baleriola, Jimena
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279726/
https://www.ncbi.nlm.nih.gov/pubmed/34276318
http://dx.doi.org/10.3389/fnint.2021.689208
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author Gamarra, María
de la Cruz, Aida
Blanco-Urrejola, Maite
Baleriola, Jimena
author_facet Gamarra, María
de la Cruz, Aida
Blanco-Urrejola, Maite
Baleriola, Jimena
author_sort Gamarra, María
collection PubMed
description Dendrites and axons can extend dozens to hundreds of centimeters away from the cell body so that a single neuron can sense and respond to thousands of stimuli. Thus, for an accurate function of dendrites and axons the neuronal proteome needs to be asymmetrically distributed within neurons. Protein asymmetry can be achieved by the transport of the protein itself or the transport of the mRNA that is then translated at target sites in neuronal processes. The latter transport mechanism implies local translation of localized mRNAs. The role of local translation in nervous system (NS) development and maintenance is well established, but recently there is growing evidence that this mechanism and its deregulation are also relevant in NS pathologies, including neurodegenerative diseases. For instance, upon pathological signals disease-related proteins can be locally synthesized in dendrites and axons. Locally synthesized proteins can exert their effects at or close to the site of translation, or they can be delivered to distal compartments like the nucleus and induce transcriptional responses that lead to neurodegeneration, nerve regeneration and other cell-wide responses. Relevant key players in the process of local protein synthesis are RNA binding proteins (RBPs), responsible for mRNA transport to neurites. Several neurological and neurodegenerative disorders, including amyotrophic lateral sclerosis or spinal motor atrophy, are characterized by mutations in genes encoding for RBPs and consequently mRNA localization and local translation are impaired. In other diseases changes in the local mRNA repertoire and altered local protein synthesis have been reported. In this review, we will discuss how deregulation of localized translation at different levels can contribute to the development and progression of nervous system pathologies.
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spelling pubmed-82797262021-07-15 Local Translation in Nervous System Pathologies Gamarra, María de la Cruz, Aida Blanco-Urrejola, Maite Baleriola, Jimena Front Integr Neurosci Neuroscience Dendrites and axons can extend dozens to hundreds of centimeters away from the cell body so that a single neuron can sense and respond to thousands of stimuli. Thus, for an accurate function of dendrites and axons the neuronal proteome needs to be asymmetrically distributed within neurons. Protein asymmetry can be achieved by the transport of the protein itself or the transport of the mRNA that is then translated at target sites in neuronal processes. The latter transport mechanism implies local translation of localized mRNAs. The role of local translation in nervous system (NS) development and maintenance is well established, but recently there is growing evidence that this mechanism and its deregulation are also relevant in NS pathologies, including neurodegenerative diseases. For instance, upon pathological signals disease-related proteins can be locally synthesized in dendrites and axons. Locally synthesized proteins can exert their effects at or close to the site of translation, or they can be delivered to distal compartments like the nucleus and induce transcriptional responses that lead to neurodegeneration, nerve regeneration and other cell-wide responses. Relevant key players in the process of local protein synthesis are RNA binding proteins (RBPs), responsible for mRNA transport to neurites. Several neurological and neurodegenerative disorders, including amyotrophic lateral sclerosis or spinal motor atrophy, are characterized by mutations in genes encoding for RBPs and consequently mRNA localization and local translation are impaired. In other diseases changes in the local mRNA repertoire and altered local protein synthesis have been reported. In this review, we will discuss how deregulation of localized translation at different levels can contribute to the development and progression of nervous system pathologies. Frontiers Media S.A. 2021-06-29 /pmc/articles/PMC8279726/ /pubmed/34276318 http://dx.doi.org/10.3389/fnint.2021.689208 Text en Copyright © 2021 Gamarra, de la Cruz, Blanco-Urrejola and Baleriola. 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
Gamarra, María
de la Cruz, Aida
Blanco-Urrejola, Maite
Baleriola, Jimena
Local Translation in Nervous System Pathologies
title Local Translation in Nervous System Pathologies
title_full Local Translation in Nervous System Pathologies
title_fullStr Local Translation in Nervous System Pathologies
title_full_unstemmed Local Translation in Nervous System Pathologies
title_short Local Translation in Nervous System Pathologies
title_sort local translation in nervous system pathologies
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279726/
https://www.ncbi.nlm.nih.gov/pubmed/34276318
http://dx.doi.org/10.3389/fnint.2021.689208
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