{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T18:47:03Z","timestamp":1792522023631,"version":"4.5.0"},"reference-count":92,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"23","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2025,6,6]]},"abstract":"<jats:p>\n            Duplication of the\n            <jats:italic toggle=\"yes\">SNCA<\/jats:italic>\n            gene (\n            <jats:italic toggle=\"yes\">SNCA<\/jats:italic>\n            <jats:sup>Dupl<\/jats:sup>\n            ), linked to elevated levels of \u03b1-synuclein (aSyn), is a genetic cause of Parkinson\u2019s disease (PD). Our prior work with human-induced pluripotent stem cell (hiPSC)\u2013derived midbrain neurons generated from patients with PD\n            <jats:italic toggle=\"yes\">SNCA<\/jats:italic>\n            <jats:sup>Dupl<\/jats:sup>\n            identified neuritic deficits, accompanied by decreased levels of cytoskeletal element \u03b2-tubulin-III (bTubIII). To explore mechanisms underlying these effects in\n            <jats:italic toggle=\"yes\">SNCA<\/jats:italic>\n            <jats:sup>Dupl<\/jats:sup>\n            neurons, we used CRISPR-Cas9 to generate isogenic control hiPSCs. Isogenic correction of\n            <jats:italic toggle=\"yes\">SNCA<\/jats:italic>\n            dosage restored\n            <jats:italic toggle=\"yes\">SNCA<\/jats:italic>\n            <jats:sup>Dupl<\/jats:sup>\n            -induced neurite defects and bTubIII levels. Multi-omics analyses revealed\n            <jats:italic toggle=\"yes\">SNCA<\/jats:italic>\n            <jats:sup>Dupl<\/jats:sup>\n            -induced alterations in neuronal differentiation, with a notable down-regulation of PAX6. Moreover,\n            <jats:italic toggle=\"yes\">SNCA<\/jats:italic>\n            <jats:sup>Dupl<\/jats:sup>\n            induced an up-regulation of vimentin. Further characterization revealed heightened vimentin truncation associated with altered distribution and organization. Similar changes in vimentin levels and truncation were observed in postmortem putamen tissue from patients with sporadic PD. Notably, targeting vimentin with okadaic acid and withaferin A restored bTubIII- and neurite-associated defects, suggesting its potential to prevent aSyn-mediated neuritic degeneration.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adq2742","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T17:58:24Z","timestamp":1749232704000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":7,"title":["Vimentin network dysregulation mediates neurite deficits in\n            <i>SNCA<\/i>\n            duplication Parkinson\u2019s patient\u2013derived midbrain neurons"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1336-2102","authenticated-orcid":true,"given":"Yanni","family":"Schneider","sequence":"first","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1898-0374","authenticated-orcid":true,"given":"Aron","family":"Koller","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Schweigert","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5440-8153","authenticated-orcid":true,"given":"Marie","family":"Andert","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7873-2644","authenticated-orcid":true,"given":"Laura","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ludwig Maximilian University M\u00fcnchen, W\u00fcrmtalstrasse 201, 81375 Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0752-6366","authenticated-orcid":true,"given":"Sydney","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas","family":"Seebauer","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Pl\u00f6tz","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4910-6263","authenticated-orcid":true,"given":"Pavel","family":"Kielkowski","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ludwig Maximilian University M\u00fcnchen, W\u00fcrmtalstrasse 201, 81375 Munich, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Winkler","sequence":"additional","affiliation":[{"name":"Department of Molecular Neurology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-N\u00fcrnberg, 91054 Erlangen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-9743","authenticated-orcid":true,"given":"Johannes C. 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