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Synucleinopathy in amyotrophic lateral sclerosis: A potential avenue for antisense therapeutics?

Roberts, B., Theunissen, F., Mastaglia, F.L., Akkari, P.A. and Flynn, L.L. (2022) Synucleinopathy in amyotrophic lateral sclerosis: A potential avenue for antisense therapeutics? International Journal of Molecular Sciences, 23 (16). Article 9364.

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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.

Item Type: Journal Article
Murdoch Affiliation(s): Centre for Molecular Medicine and Innovative Therapeutics
Publisher: MDPI
Copyright: © 2022 by the authors
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