{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T20:13:21Z","timestamp":1793650401085,"version":"4.5.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T00:00:00Z","timestamp":1693180800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Parkinson\u2019s disease is characterised by the deposition in the brain of amyloid aggregates of \u03b1-synuclein. The surfaces of these amyloid aggregates can catalyse the formation of new aggregates, giving rise to a positive feedback mechanism responsible for the rapid proliferation of \u03b1-synuclein deposits. We report a procedure to enhance the potency of a small molecule to inhibit the aggregate proliferation process using a combination of <jats:italic>in silico<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> methods. The optimized small molecule shows potency already at a compound:protein stoichiometry of 1:20. These results illustrate a strategy to accelerate the optimisation of small molecules against \u03b1-synuclein aggregation by targeting secondary nucleation.<\/jats:p>","DOI":"10.3389\/fmolb.2023.1155753","type":"journal-article","created":{"date-parts":[[2023,8,28]],"date-time":"2023-08-28T13:21:50Z","timestamp":1693228910000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Optimization of a small molecule inhibitor of secondary nucleation in \u03b1-synuclein aggregation"],"prefix":"10.3389","volume":"10","author":[{"given":"Roxine","family":"Staats","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z. 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