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Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases

The main goal of this review is to provide an updated overview of the involvement of the RNA-binding protein (RBP) HuD, encoded by the ELAVL4 gene, in nervous system development, maintenance, and function, and its emerging role in nervous system diseases. A particular focus is on recent studies repo...

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Autores principales: Silvestri, Beatrice, Mochi, Michela, Garone, Maria Giovanna, Rosa, Alessandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736382/
https://www.ncbi.nlm.nih.gov/pubmed/36498933
http://dx.doi.org/10.3390/ijms232314606
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author Silvestri, Beatrice
Mochi, Michela
Garone, Maria Giovanna
Rosa, Alessandro
author_facet Silvestri, Beatrice
Mochi, Michela
Garone, Maria Giovanna
Rosa, Alessandro
author_sort Silvestri, Beatrice
collection PubMed
description The main goal of this review is to provide an updated overview of the involvement of the RNA-binding protein (RBP) HuD, encoded by the ELAVL4 gene, in nervous system development, maintenance, and function, and its emerging role in nervous system diseases. A particular focus is on recent studies reporting altered HuD levels, or activity, in disease models and patients. Substantial evidence suggests HuD involvement in Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). Interestingly, while possible disease-causing mutations in the ELAVL4 gene remain elusive, a common theme in these diseases seems to be the altered regulation of HuD at multiple steps, including post-transcriptional and post-translational levels. In turn, the changed activity of HuD can have profound implications for its target transcripts, which are overly stabilized in case of HuD gain of function (as proposed in PD and ALS) or reduced in case of decreased HuD binding (as suggested by some studies in AD). Moreover, the recent discovery that HuD is a component of pathological cytoplasmic inclusion in both familial and sporadic ALS patients might help uncover the common molecular mechanisms underlying such complex diseases. We believe that deepening our understanding of the involvement of HuD in neurodegeneration could help developing new diagnostic and therapeutic tools.
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spelling pubmed-97363822022-12-11 Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases Silvestri, Beatrice Mochi, Michela Garone, Maria Giovanna Rosa, Alessandro Int J Mol Sci Review The main goal of this review is to provide an updated overview of the involvement of the RNA-binding protein (RBP) HuD, encoded by the ELAVL4 gene, in nervous system development, maintenance, and function, and its emerging role in nervous system diseases. A particular focus is on recent studies reporting altered HuD levels, or activity, in disease models and patients. Substantial evidence suggests HuD involvement in Parkinson’s disease (PD), Alzheimer’s disease (AD), and amyotrophic lateral sclerosis (ALS). Interestingly, while possible disease-causing mutations in the ELAVL4 gene remain elusive, a common theme in these diseases seems to be the altered regulation of HuD at multiple steps, including post-transcriptional and post-translational levels. In turn, the changed activity of HuD can have profound implications for its target transcripts, which are overly stabilized in case of HuD gain of function (as proposed in PD and ALS) or reduced in case of decreased HuD binding (as suggested by some studies in AD). Moreover, the recent discovery that HuD is a component of pathological cytoplasmic inclusion in both familial and sporadic ALS patients might help uncover the common molecular mechanisms underlying such complex diseases. We believe that deepening our understanding of the involvement of HuD in neurodegeneration could help developing new diagnostic and therapeutic tools. MDPI 2022-11-23 /pmc/articles/PMC9736382/ /pubmed/36498933 http://dx.doi.org/10.3390/ijms232314606 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
Silvestri, Beatrice
Mochi, Michela
Garone, Maria Giovanna
Rosa, Alessandro
Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
title Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
title_full Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
title_fullStr Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
title_full_unstemmed Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
title_short Emerging Roles for the RNA-Binding Protein HuD (ELAVL4) in Nervous System Diseases
title_sort emerging roles for the rna-binding protein hud (elavl4) in nervous system diseases
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9736382/
https://www.ncbi.nlm.nih.gov/pubmed/36498933
http://dx.doi.org/10.3390/ijms232314606
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