{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T08:10:22Z","timestamp":1768551022877,"version":"3.49.0"},"reference-count":138,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T00:00:00Z","timestamp":1603238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Alpha-synuclein (\u03b1-Syn) is a 140-amino acid (aa) protein encoded by the Synuclein alpha SNCA gene. It is the synaptic protein associated with Parkinson\u2019s disease (PD) and is the most highly expressed protein in the Lewy bodies associated with PD and other alpha synucleopathies, including Lewy body dementia (LBD) and multiple system atrophy (MSA). Iron deposits are present in the core of Lewy bodies, and there are reports suggesting that divalent metal ions including Cu2+ and Fe2+ enhance the aggregation of \u03b1-Syn. Differential expression of \u03b1-Syn is associated with alcohol use disorder (AUD), and specific genetic variants contribute to the risk for alcoholism, including alcohol craving. Spliced variants of \u03b1-Syn, leading to the expression of several shorter forms which are more prone to aggregation, are associated with both PD and AUD, and common transcript variants may be able to predict at-risk populations for some movement disorders or subtypes of PD, including secondary Parkinsonism. Both PD and AUD are associated with liver and brain iron dyshomeostasis. Research over the past decade has shown that \u03b1-Syn has iron import functions with an ability to oxidize the Fe3+ form of iron to Fe2+ to facilitate its entry into cells. Our prior research has identified an iron-responsive element (IRE) in the 5\u2019 untranslated region (5\u2019UTR) of \u03b1-Syn mRNA, and we have used the \u03b1-Syn 5\u2019UTR to screen for small molecules that modulate its expression in the H4 neuronal cell line. These screens have led us to identify several interesting small molecules capable of both decreasing and increasing \u03b1-Syn expression and that may have the potential, together with the recently described mesenchymal stem cell therapies, to normalize \u03b1-Syn expression in different regions of the alcoholic and PD brain.<\/jats:p>","DOI":"10.3390\/biom10101465","type":"journal-article","created":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T20:51:00Z","timestamp":1603399860000},"page":"1465","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Alpha-Synuclein in Alcohol Use Disorder, Connections with Parkinson\u2019s Disease and Potential Therapeutic Role of 5\u2019 Untranslated Region-Directed Small Molecules"],"prefix":"10.3390","volume":"10","author":[{"given":"Catherine M.","family":"Cahill","sequence":"first","affiliation":[{"name":"Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rozaleen","family":"Aleyadeh","sequence":"additional","affiliation":[{"name":"Weill Cornell Medicine-Qatar, Qatar Foundation, Doha 24144, Qatar"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Clinical Psychology, Qilu Hospital of Shandong University, Qingdao 266011, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Changning","family":"Wang","sequence":"additional","affiliation":[{"name":"Athinoula A. Martinos Center for Biomedical Imaging Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack T.","family":"Rogers","sequence":"additional","affiliation":[{"name":"Neurochemistry Laboratory, Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1021\/acschemneuro.5b00204","article-title":"Non-Amyloid-beta Component of Human alpha-Synuclein Oligomers Induces Formation of New Abeta Oligomers: Insight into the Mechanisms That Link Parkinson\u2019s and Alzheimer\u2019s Diseases","volume":"7","author":"Miller","year":"2016","journal-title":"ACS Chem. 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