{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:54:04Z","timestamp":1791464044875,"version":"4.3.4"},"reference-count":81,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["2003710"],"award-info":[{"award-number":["2003710"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    \u03b1\u2010Synuclein is a presynaptic protein that has been extensively studied for its role in Parkinson's disease. Multiplication and missense variants in the gene encoding \u03b1\u2010synuclein are causes of familial PD, and aggregated \u03b1\u2010synuclein is a major component of Lewy bodies and Lewy neurites, the histopathological hallmark of the disease. However, the native function of \u03b1\u2010synuclein remains unclear, though several lines of evidence suggest it modulates presynaptic function. \u03b1\u2010Synuclein binds the vesicular SNARE protein synaptobrevin\u20102\/VAMP2, and increased levels of \u03b1\u2010synuclein potentiate SNARE complex levels without impacting exocytic rate. Given the essential role of synaptobrevin\u20102 in synaptic function we sought to examine how increased expression of \u03b1\u2010synuclein, at levels observed in familial synucleinopathies with\n                    <jats:italic>SNCA<\/jats:italic>\n                    triplication, impacts the trafficking of this essential SNARE protein. Modest (approximately 2\u2010fold) overexpression of \u03b1\u2010synuclein in cultured murine hippocampal neurons caused a slowing in the endocytic retrieval of synaptobrevin\u20102, without impacting either the targeting of the protein to synapses or altering endocytosis. We also show that \u03b1\u2010synuclein is not working antagonistically with the synaptobrevin\u20102 chaperone synaptophysin, and likely acts at least partially via direct binding to synaptobrevin\u20102. Finally, increased expression of \u03b1\u2010synuclein induces synaptic depression upon repeated neuronal depolarisation, in a manner requiring binding to synaptobrevin\u20102. We reveal \u03b1\u2010synuclein as a modulator of synaptobrevin\u20102 endocytic trafficking and highlight perturbed SNARE protein trafficking as a potential contributor to synaptic dysfunction and neuronal health in Parkinson's disease.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70568-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.70568","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:04:57Z","timestamp":1791461097000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Increased Expression of \u03b1\u2010Synuclein Impairs Trafficking of the Essential\n                    <scp>SNARE<\/scp>\n                    Protein Synaptobrevin\u20102"],"prefix":"10.1111","volume":"170","author":[{"given":"Elyas H.","family":"Arvell","sequence":"first","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5276-707X","authenticated-orcid":false,"given":"James P.","family":"Carroll","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Saito","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0311-6474","authenticated-orcid":false,"given":"Holly","family":"Melland","sequence":"additional","affiliation":[{"name":"Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Faculty of Pharmacy and Pharmaceutical Sciences Monash University  Parkville Victoria Australia"},{"name":"Neuromedicines Discovery Centre Monash University  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1710-002X","authenticated-orcid":false,"given":"Ranjith R.","family":"Unnithan","sequence":"additional","affiliation":[{"name":"Department of Electrical and Electronic Engineering The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1445-8704","authenticated-orcid":false,"given":"Chris","family":"French","sequence":"additional","affiliation":[{"name":"Department of Medicine The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9965-2847","authenticated-orcid":false,"given":"Danny M.","family":"Hatters","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2281-3160","authenticated-orcid":false,"given":"Sarah L.","family":"Gordon","sequence":"additional","affiliation":[{"name":"The Florey Institute of Neuroscience and Mental Health The University of Melbourne  Parkville Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0896-6273(00)80886-7","article-title":"Mice Lacking Alpha\u2010Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System","volume":"25","author":"Abeliovich A.","year":"2000","journal-title":"Neuron"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1860\u201025.2026"},{"key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"11116","DOI":"10.1073\/pnas.1903054116","article-title":"Synapsins Regulate Alpha\u2010Synuclein Functions","volume":"116","author":"Atias M.","year":"2019","journal-title":"Proceedings of the National Academy of Sciences of the United States of 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