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Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?

Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease classified as both a neurodegenerative and neuromuscular disorder. With a complex aetiology and no current cure for ALS, broadening the understanding of disease pathology and therapeutic avenues is required to pr...

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Autores principales: Roberts, Bradley, Theunissen, Frances, Mastaglia, Francis L., Akkari, P. Anthony, Flynn, Loren L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409035/
https://www.ncbi.nlm.nih.gov/pubmed/36012622
http://dx.doi.org/10.3390/ijms23169364
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author Roberts, Bradley
Theunissen, Frances
Mastaglia, Francis L.
Akkari, P. Anthony
Flynn, Loren L.
author_facet Roberts, Bradley
Theunissen, Frances
Mastaglia, Francis L.
Akkari, P. Anthony
Flynn, Loren L.
author_sort Roberts, Bradley
collection PubMed
description Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease classified as both a neurodegenerative and neuromuscular disorder. With a complex aetiology and no current cure for ALS, broadening the understanding of disease pathology and therapeutic avenues is required to progress with patient care. Alpha-synuclein (αSyn) is a hallmark for disease in neurodegenerative disorders, such as Parkinson’s disease, Lewy body dementia, and multiple system atrophy. A growing body of evidence now suggests that αSyn may also play a pathological role in ALS, with αSyn-positive Lewy bodies co-aggregating alongside known ALS pathogenic proteins, such as SOD1 and TDP-43. This review endeavours to capture the scope of literature regarding the aetiology and development of ALS and its commonalities with “synucleinopathy disorders”. We will discuss the involvement of αSyn in ALS and motor neuron disease pathology, and the current theories and strategies for therapeutics in ALS treatment, as well as those targeting αSyn for synucleinopathies, with a core focus on small molecule RNA technologies.
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spelling pubmed-94090352022-08-26 Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics? Roberts, Bradley Theunissen, Frances Mastaglia, Francis L. Akkari, P. Anthony Flynn, Loren L. Int J Mol Sci Review Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease classified as both a neurodegenerative and neuromuscular disorder. With a complex aetiology and no current cure for ALS, broadening the understanding of disease pathology and therapeutic avenues is required to progress with patient care. Alpha-synuclein (αSyn) is a hallmark for disease in neurodegenerative disorders, such as Parkinson’s disease, Lewy body dementia, and multiple system atrophy. A growing body of evidence now suggests that αSyn may also play a pathological role in ALS, with αSyn-positive Lewy bodies co-aggregating alongside known ALS pathogenic proteins, such as SOD1 and TDP-43. This review endeavours to capture the scope of literature regarding the aetiology and development of ALS and its commonalities with “synucleinopathy disorders”. We will discuss the involvement of αSyn in ALS and motor neuron disease pathology, and the current theories and strategies for therapeutics in ALS treatment, as well as those targeting αSyn for synucleinopathies, with a core focus on small molecule RNA technologies. MDPI 2022-08-19 /pmc/articles/PMC9409035/ /pubmed/36012622 http://dx.doi.org/10.3390/ijms23169364 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
Roberts, Bradley
Theunissen, Frances
Mastaglia, Francis L.
Akkari, P. Anthony
Flynn, Loren L.
Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?
title Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?
title_full Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?
title_fullStr Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?
title_full_unstemmed Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?
title_short Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?
title_sort synucleinopathy in amyotrophic lateral sclerosis: a potential avenue for antisense therapeutics?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9409035/
https://www.ncbi.nlm.nih.gov/pubmed/36012622
http://dx.doi.org/10.3390/ijms23169364
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