{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T19:46:14Z","timestamp":1792611974407,"version":"4.5.0"},"reference-count":61,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471355"],"award-info":[{"award-number":["82471355"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Atherosclerosis, recognized as a prototypical age\u2010associated vascular disease, is driven by macrophage foam cell formation. Individuals with Parkinson's disease (PD) exhibit an elevated risk for stroke. While \u03b1\u2010synuclein (\u03b1\u2010Syn) is known for its neuronal role in PD, its presence in the circulation and potential vascular effects remain unexplored. Here, we identify \u03b1\u2010Syn as a previously unrecognized circulating factor that promotes atherosclerosis. \u03b1\u2010Syn was detected in human atherosclerotic plaques. Genetic deletion of \u03b1\u2010Syn reduced atherosclerotic lesion size and macrophage lipid accumulation in a mouse model of atherosclerosis induced by overexpression of proprotein convertase subtilisin\/kexin type 9 (PCSK9). On the contrary, administration of exogenous \u03b1\u2010Syn accelerated atherosclerosis in Apolipoprotein E knockout (\n                    <jats:italic>Apoe<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) mice. Mechanistically, \u03b1\u2010Syn promoted macrophage foam cell formation by impairing autophagic flux, accompanied by activation of PI3K\u2010mTOR signaling. Proteomic analysis identified the membrane raft protein flotillin\u20101 (FLOT1) as a candidate upstream mediator.\n                    <jats:italic>Flot1<\/jats:italic>\n                    knockdown reduced \u03b1\u2010Syn internalization, PI3K phosphorylation, autophagy impairment, and lipid accumulation, while pharmacological inhibition of PI3K or mTOR attenuated the effects of \u03b1\u2010Syn. Together, these findings identify a FLOT1\u2010associated pathway through which extracellular \u03b1\u2010Syn disrupts macrophage autophagy and promotes atherosclerosis.\n                  <\/jats:p>","DOI":"10.1111\/acel.70713","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:26:41Z","timestamp":1790659601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b1\u2010Synuclein Promotes Atherosclerosis by Impairing Macrophage Autophagic Flux"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-8543-4810","authenticated-orcid":false,"given":"Mengting","family":"Qin","sequence":"first","affiliation":[{"name":"Department of Neurology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan 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