{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T01:27:57Z","timestamp":1789694877106,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T00:00:00Z","timestamp":1749859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteins"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Neurodegenerative diseases such as Parkinson's disease are characterized by the pathological aggregation of \u03b1\u2010synuclein. Targeting \u03b1\u2010synuclein aggregation through natural bioactive compounds offers a promising therapeutic strategy. In this study, sulfur\u2010containing compounds derived from <jats:styled-content style=\"fixed-case\">\n<jats:italic>Allium sativum<\/jats:italic>\n<\/jats:styled-content> were evaluated for their drug\u2010likeness, pharmacokinetic properties, and ability to inhibit \u03b1\u2010synuclein aggregation using a combination of in silico and in\u00a0vitro approaches. ADMET profiling indicated high gastrointestinal absorption for nine compounds, supporting their drug\u2010like properties. Six compounds were predicted to cross the blood\u2013brain barrier, suggesting potential efficacy in the central nervous system. Molecular docking identified alliin, allicin, E\u2010ajoene, and diallyl disulfide as top binders to \u03b1\u2010synuclein, forming stable interactions with key aggregation\u2010prone regions. Molecular dynamics simulations over 100\u2009ns confirmed the structural stability of alliin\u2013 and allicin\u2013\u03b1\u2010synuclein complexes, with minimal residue fluctuations and persistent hydrogen bonding. MM\u2010GBSA binding energy analysis corroborated these results, showing favorable binding free energies, particularly for alliin and E\u2010ajoene. Principal component analysis (PCA) further supported the role of alliin in stabilizing \u03b1\u2010synuclein dynamics. In\u00a0vitro cellular assays further validated these computational findings. Using an SH\u2010SY5Y cell\u2010based \u03b1\u2010synuclein aggregation model, treatment with alliin and allicin significantly reduced \u03b1\u2010synuclein aggregation. Furthermore, MTT\u2010based cytotoxicity assays in SH\u2010SY5Y neuroblastoma cells overexpressing \u03b1\u2010synuclein revealed that alliin and allicin conferred notable cytoprotective effects by reducing \u03b1\u2010synuclein\u2010induced toxicity. Taken together, these findings highlight alliin and allicin as potent lead compounds that not only bind and stabilize \u03b1\u2010synuclein but also attenuate its aggregation and associated cytotoxicity.<\/jats:p>","DOI":"10.1002\/prot.70000","type":"journal-article","created":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T08:14:58Z","timestamp":1749888898000},"page":"1905-1920","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp><i>Allium sativum<\/i><\/scp>\u2010Derived Alliin and Allicin Stably Bind to \u03b1\u2010Synuclein and Prevent Its Cytotoxic Aggregation"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-5238","authenticated-orcid":false,"given":"S. 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