{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:44:34Z","timestamp":1791996274795,"version":"4.4.0"},"reference-count":234,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,19]],"date-time":"2022-08-19T00:00:00Z","timestamp":1660867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 (\u03b1Syn) is a hallmark for disease in neurodegenerative disorders, such as Parkinson\u2019s disease, Lewy body dementia, and multiple system atrophy. A growing body of evidence now suggests that \u03b1Syn may also play a pathological role in ALS, with \u03b1Syn-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 \u201csynucleinopathy disorders\u201d. We will discuss the involvement of \u03b1Syn in ALS and motor neuron disease pathology, and the current theories and strategies for therapeutics in ALS treatment, as well as those targeting \u03b1Syn for synucleinopathies, with a core focus on small molecule RNA technologies.<\/jats:p>","DOI":"10.3390\/ijms23169364","type":"journal-article","created":{"date-parts":[[2022,8,21]],"date-time":"2022-08-21T22:23:13Z","timestamp":1661120593000},"page":"9364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Synucleinopathy in Amyotrophic Lateral Sclerosis: A Potential Avenue for Antisense Therapeutics?"],"prefix":"10.3390","volume":"23","author":[{"given":"Bradley","family":"Roberts","sequence":"first","affiliation":[{"name":"The Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Theunissen","sequence":"additional","affiliation":[{"name":"The Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis L.","family":"Mastaglia","sequence":"additional","affiliation":[{"name":"The Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA 6150, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Anthony","family":"Akkari","sequence":"additional","affiliation":[{"name":"The Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Crawley, WA 6009, Australia"},{"name":"Division of Neurology, Duke University Medical Centre, Duke University, Durham, NC 27708, USA"},{"name":"Black Swan Pharmaceuticals, Wake Forrest, NC 27587, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5249-547X","authenticated-orcid":false,"given":"Loren L.","family":"Flynn","sequence":"additional","affiliation":[{"name":"The Perron Institute for Neurological and Translational Science, Nedlands, WA 6009, Australia"},{"name":"Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA 6150, Australia"},{"name":"Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Crawley, WA 6009, Australia"},{"name":"Black Swan Pharmaceuticals, Wake Forrest, NC 27587, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nrn3430","article-title":"The changing scene of amyotrophic lateral sclerosis","volume":"14","author":"Robberecht","year":"2013","journal-title":"Nat. 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