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Fyn kinase physically associates with Tau and regulates subcellular distribution. Here, we assessed whether pharmacological Fyn inhibition alters Tauopathy. In P301S transgenic mice, chronic Fyn inhibition prevented deficits in spatial memory and passive avoidance learning. The behavioral improvement was coupled with reduced accumulation of phospho-Tau in the hippocampus, with reductions in glial activation and with recovery of presynaptic markers. We extended this analysis to a trauma model in which very mild repetitive closed head injury was paired with chronic variable stress over 2\u2009weeks to produce persistent memory deficits and Tau accumulation. In this model, Fyn inhibition beginning 24\u2009h after the trauma ended rescued memory performance and reduced phospho-Tau accumulation. Thus, inhibition of Fyn kinase may have therapeutic benefit in clinical Tauopathies.<\/jats:p>","DOI":"10.1186\/s40478-020-00976-9","type":"journal-article","created":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T07:53:05Z","timestamp":1593589985000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy"],"prefix":"10.1186","volume":"8","author":[{"given":"Si Jie","family":"Tang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arman","family":"Fesharaki-Zadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyuki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah Helena","family":"Nies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levi M.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anin","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annabel","family":"Chyung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Chiasseu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8188-3092","authenticated-orcid":false,"given":"Stephen M.","family":"Strittmatter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,1]]},"reference":[{"key":"976_CR1","doi-asserted-by":"publisher","unstructured":"Apicco DJ, Ash PEA, Maziuk B, LeBlang C, Medalla M, Al Abdullatif A, Ferragud A, Botelho E, Ballance HI, Dhawan U et al (2018) Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo. 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