{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:01:19Z","timestamp":1791511279177,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":["82201395"],"award-info":[{"award-number":["82201395"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271447"],"award-info":[{"award-number":["82271447"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>The aggregation of \u03b1\u2010synuclein (\u03b1\u2010syn) is a central event in Parkinson's disease (PD) pathogenesis. However, the cellular factors that initiate and accelerate the process are not fully understood. Synaptogyrin\u20103 (SYNGR3) is a synaptic vesicle protein whose role in \u03b1\u2010syn pathology remains unexplored. This study investigated whether SYNGR3 is a key factor triggering the pathological process of PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study investigated the expression of SYNGR3 in the brains of transgenic A53T \u03b1\u2010syn mutant mouse line M83 (TgA53T) PD model mice using Western blot. The direct interaction between SYNGR3 and \u03b1\u2010syn was assessed by GST pull\u2010down assays. This study examined the effect of SYNGR3 on \u03b1\u2010syn aggregation kinetics and fibril stability in\u00a0vitro through the thioflavin T (Th T) assays and proteinase K (PK) digestion. By overexpressing or knocking down SYNGR3 in HEK\u2010293 cells stably transfected with \u03b1\u2010syn, primary neurons, and TgA53T mice, the effects of enhanced or deficient function of SYNGR3 on \u03b1\u2010syn pathology, synaptic integrity, mitochondrial function, and motor behavior were evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SYNGR3 levels were significantly elevated in an age\u2010dependent manner in the striatum of TgA53T mice. The study found that SYNGR3 directly interacts with the central region of \u03b1\u2010syn and accelerates its aggregation into fibrils that are more resistant to PK digestion. Overexpression of SYNGR3 exacerbated \u03b1\u2010syn aggregation, synaptic protein loss, mitochondrial dysfunction, and apoptosis in cellular models. In\u00a0vivo, SYNGR3 intensified \u03b1\u2010syn pathology, dopaminergic neurodegeneration, and PD\u2010like motor deficits. Conversely, knockdown of SYNGR3 effectively alleviated these pathological and behavioral impairments.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study identifies SYNGR3 as a novel and critical promoter of \u03b1\u2010syn aggregation and neurotoxicity. These findings establish SYNGR3 as a key contributor to PD pathogenesis and highlight its potential as a therapeutic target for intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70842","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T05:27:16Z","timestamp":1774416436000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>SYNGR3<\/scp>\n                    Accelerates \u03b1\u2010Synuclein Aggregation and Neurodegeneration in Parkinson's Disease"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6800-4418","authenticated-orcid":false,"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaolong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziku","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhichao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Tan","sequence":"additional","affiliation":[{"name":"Geriatric Hospital Affiliated to Wuhan University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6708-1472","authenticated-orcid":false,"given":"Zhentao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Renmin Hospital of Wuhan University  Wuhan China"},{"name":"Taikang Center for Life and Medical Sciences Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra2401857"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2019-322338"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00030-2"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.04.004"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.12.023"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00368-6"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adp3645"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adj1092"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2021.736978"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac171"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2023.102462"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2024.01.002"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26479"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12563"},{"key":"e_1_2_12_16_1","first-page":"103","volume-title":"Tetraspan Vesicle Membrane Proteins: Synthesis, Subcellular Localization, and Functional Properties [M\/OL]\/\/ International Review of Cytology: 214","author":"H\u00fcbner K.","year":"2002"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390050795"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.40744"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.01.022"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.12.016"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4559-08.2009"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2014.143"},{"key":"e_1_2_12_23_1","first-page":"562","article-title":"Preparation of Dissociated Mouse Cortical Neuron Cultures","volume":"10","author":"Hilgenberg L. 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