{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:20:30Z","timestamp":1787170830550,"version":"build-2736575974"},"reference-count":40,"publisher":"Society for Neuroscience","issue":"4","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017236","name":"Huffington Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017236","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["eNeuro"],"accepted":{"date-parts":[[2025,2,12]]},"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:p>\n                    Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor symptoms. Its pathological hallmarks include the accumulation of misfolded alpha-synuclein (\u03b1-Syn) in Lewy bodies and Lewy neurites. Phosphorylation of \u03b1-Syn is a prominent feature of these inclusions, but its role in disease pathogenesis remains unclear. To identify the role of \u03b1-Syn phosphorylation in synucleinopathy, we generated two\n                    <jats:italic>Snca<\/jats:italic>\n                    knock-in (KI) mouse models carrying phosphomimetic mutations at SncaY39 or SncaS129 (\n                    <jats:italic>\n                      Snca\n                      <jats:sup>Y39E<\/jats:sup>\n                    <\/jats:italic>\n                    or\n                    <jats:italic>\n                      Snca\n                      <jats:sup>S129D<\/jats:sup>\n                    <\/jats:italic>\n                    ) which manipulated epitopes phosphorylated in the PD brain. Both\n                    <jats:italic>\n                      Snca\n                      <jats:sup>Y39E<\/jats:sup>\n                    <\/jats:italic>\n                    and\n                    <jats:italic>\n                      Snca\n                      <jats:sup>S129D<\/jats:sup>\n                    <\/jats:italic>\n                    KI mice displayed increased \u03b1-Syn phosphorylation, enhanced oligomer formation, and a shift of \u03b1-Syn localization from membrane-bound to cytoplasm. However, neurodegeneration in the substantia nigra was not observed up to 24\u2005months of age. These findings demonstrate that mimicking the phosphorylation of Y39 or S129 can induce endogenous \u03b1-Syn phosphorylation. Still, a single phosphomimetic mutation alone is insufficient to induce PD-like behavior and pathology in the mouse's lifespan. Overall, our study provides a mouse model for investigating the role of phosphorylation at Y39 and S129 \u03b1-Syn epitopes in vivo.\n                  <\/jats:p>","DOI":"10.1523\/eneuro.0357-24.2025","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T13:50:25Z","timestamp":1743429025000},"page":"ENEURO.0357-24.2025","source":"Crossref","is-referenced-by-count":4,"title":["Alpha-Synuclein Phosphomimetic Y39E and S129D Knock-In Mice Show Cytosolic Alpha-Synuclein Localization without Developing Neurodegeneration or Motor Deficits"],"prefix":"10.1523","volume":"12","author":[{"given":"YoungDoo","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhupesh","family":"Vaidya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"McInnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huda Y.","family":"Zoghbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2025,3,31]]},"reference":[{"key":"2025041110500839000_12.4.ENEURO.0357-24.2025.1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600933200"},{"key":"2025041110500839000_12.4.ENEURO.0357-24.2025.2","first-page":"879","article-title":"Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson's disease and dementia with Lewy 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