{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T02:47:45Z","timestamp":1788058065979,"version":"build-2784847793"},"reference-count":236,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T00:00:00Z","timestamp":1731196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"the National Science Centre, Poland","doi-asserted-by":"publisher","award":["2019\/32\/C\/NZ4\/00455"],"award-info":[{"award-number":["2019\/32\/C\/NZ4\/00455"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alpha-synuclein (\u03b1-syn) is a 140-amino-acid, intrinsically disordered, soluble protein that is abundantly present in the brain. It plays a crucial role in maintaining cellular structures and organelle functions, particularly in supporting synaptic plasticity and regulating neurotransmitter turnover. However, for reasons not yet fully understood, \u03b1-syn can lose its physiological role and begin to aggregate. This altered \u03b1-syn disrupts dopaminergic transmission and causes both presynaptic and postsynaptic dysfunction, ultimately leading to cell death. A group of neurodegenerative diseases known as \u03b1-synucleinopathies is characterized by the intracellular accumulation of \u03b1-syn deposits in specific neuronal and glial cells within certain brain regions. In addition to Parkinson\u2019s disease (PD), these conditions include dementia with Lewy bodies (DLBs), multiple system atrophy (MSA), pure autonomic failure (PAF), and REM sleep behavior disorder (RBD). Given that these disorders are associated with \u03b1-syn-related neuroinflammation\u2014and considering that SARS-CoV-2 infection has been shown to affect the nervous system, with COVID-19 patients experiencing neurological symptoms\u2014it has been proposed that COVID-19 may contribute to neurodegeneration in PD and other \u03b1-synucleinopathies by promoting \u03b1-syn misfolding and aggregation. In this review, we focus on whether SARS-CoV-2 could act as an environmental trigger that facilitates the onset or progression of \u03b1-synucleinopathies. Specifically, we present new evidence on the potential role of SARS-CoV-2 in modulating \u03b1-syn function and discuss the causal relationship between SARS-CoV-2 infection and the development of parkinsonism-like symptoms.<\/jats:p>","DOI":"10.3390\/ijms252212079","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"12079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["SARS-CoV-2 Infection and Alpha-Synucleinopathies: Potential Links and Underlying Mechanisms"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4170-9732","authenticated-orcid":false,"given":"Joanna Agata","family":"Motyl","sequence":"first","affiliation":[{"name":"Department of Hybrid Microbiosystems Engineering, Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, Ks. Trojdena 4 St., 02-109 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gra\u017cyna","family":"Gromadzka","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, Faculty of Medicine, Collegium Medicum, Cardinal Stefan Wyszynski University, W\u00f3ycickiego 1\/3, 01-938 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7541-1571","authenticated-orcid":false,"given":"Grzegorz Arkadiusz","family":"Czapski","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6867-9377","authenticated-orcid":false,"given":"Agata","family":"Adamczyk","sequence":"additional","affiliation":[{"name":"Department of Cellular Signalling, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/s41419-023-05672-9","article-title":"Alpha-Synuclein in Parkinson\u2019s Disease and Other Synucleinopathies: From Overt Neurodegeneration Back to Early Synaptic Dysfunction","volume":"14","author":"Calabresi","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1080\/10790268.2018.1557863","article-title":"Spinal Cord Involvement in Lewy Body-Related \u03b1-Synucleinopathies","volume":"43","author":"Nardone","year":"2020","journal-title":"J. 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