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Through RNA sequencing analysis, we identified significant upregulation of circ_0005654 (derived from the PRDM5 gene) in PD patients. Functional studies demonstrated that circ_0005654 overexpression promotes \u03b1\u2010Syn accumulation through a dual regulatory mechanism: (1) direct enhancement of its transcriptional\/translational activation of \u03b1\u2010Syn and (2) indirect suppression of autophagic clearance via miR\u2010588 sequestration\u2010mediated inhibition of the p62\u2010dependent autophagy pathway. Specifically, circ_0005654 functions as a molecular sponge for miR\u2010588, thereby coordinately enhancing \u03b1\u2010Syn synthesis while impairing its degradation. This study not only establishes the functional role of circRNAs in PD pathogenesis but also elucidates circ_0005654 as a promising therapeutic candidate for targeted modulation of \u03b1\u2010Syn aggregation.<\/jats:p>","DOI":"10.1096\/fj.202500556r","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T05:41:27Z","timestamp":1748583687000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["circ_0005654 as a Sponge of the\n                    <scp>miR<\/scp>\n                    \u2010588 Dual Pathway to Promote \u03b1\u2010Synuclein Expression"],"prefix":"10.1096","volume":"39","author":[{"given":"Jiang","family":"Lei","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Guangxi Medical University  Nanning China"},{"name":"Department of Neurology, Guangxi Hospital Division of the First Affiliated Hospital Sun Yat\u2010Sen University  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