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However, the impact of chiral selectivity on \u03b1\u2010syn aggregation and its regulatory mechanisms remain ambiguous. In this work, it is synthesized chiral carbon nanodots (CNDs), including L\u2010CNDs, D\u2010CNDs, and DL\u2010CNDs, and found that D\u2010CNDs exhibited the most potent inhibitory effect on \u03b1\u2010syn aggregation. \u00b9H\u2010\u00b9\u2075N heteronuclear single quantum coherence nuclear magnetic resonance spectroscopy revealed that CNDs primarily interact with \u03b1\u2010syn through electrostatic interactions, with D\u2010CNDs specifically targeting key aggregation\u2010prone residues, thereby disrupting \u03b2\u2010sheet formation and reducing fibril assembly. In contrast, L\u2010CNDs and DL\u2010CNDs exhibited limited inhibitory effects, attributed to their weak affinity for the non\u2010amyloid\u2010\u03b2 component region. Moreover, CNDs efficiently crossed the blood\u2010brain barrier, and D\u2010CNDs significantly reduced \u03b1\u2010syn accumulation, alleviated neuronal damage, and ameliorated cognitive function. This work underlines the critical role of chirality in modulating \u03b1\u2010syn aggregation and provides a novel strategy for developing enantiomer\u2010selective inhibitors for PD therapy.<\/jats:p>","DOI":"10.1002\/smtd.202500557","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T04:12:24Z","timestamp":1747282344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chiral Carbon Nanodots Modulate \u03b1\u2010Synuclein Homeostasis to Combat Parkinson's Disease"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1714-9506","authenticated-orcid":false,"given":"Yurong","family":"Han","sequence":"first","affiliation":[{"name":"Changchun Institute of Applied Chemistry Chinese Academy of Sciences  Changchun Jilin 130022 China"},{"name":"School of Applied Chemistry and Engineering University of Science and Technology of China  Hefei Anhui 230026 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