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Here, we tailored a nanochaperone (\u03b1S\u2010nChap) for \u03b1\u2010synuclein to regulate its assembly. The \u03b1S\u2010nChap is capable of i)\u2005specifically recognizing \u03b1\u2010synuclein; ii)\u2005dynamically capturing and stabilizing monomeric \u03b1\u2010synuclein and retarding oligomerization; iii)\u2005tightly capturing oligomeric \u03b1\u2010synuclein to prevent fibrillization; and iv)\u2005transporting \u03b1\u2010synuclein oligomers to the lysosomal degradation system. The regulation of \u03b1\u2010synuclein assembly by \u03b1S\u2010nChap was studied in vitro. Moreover, the role of \u03b1S\u2010nChap preventing \u03b1\u2010synuclein pathology in cells and protecting neurons from apoptosis was investigated. The strategy of tailoring a nanochaperone to regulate aberrant assembly of pathogenic proteins provides important insights into protein misfolding diseases. We foresee that \u03b1S\u2010nChap has therapeutic value for Parkinson's disease.<\/jats:p>","DOI":"10.1002\/anie.202200192","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T22:09:25Z","timestamp":1646086165000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Tailoring a Nanochaperone to Regulate \u03b1\u2010Synuclein Assembly"],"prefix":"10.1002","volume":"61","author":[{"given":"Xiaohui","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Functional Polymer Materials of Ministry of Education State Key Laboratory of Medicinal Chemical Biology Institute of Polymer Chemistry and College of Chemistry Nankai University  Tianjin 300071 P. R. 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