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Mechanistically, loss of Rhoa in microglia triggers Src activation and Src-mediated Tnf production, leading to excitotoxic glutamate secretion. Inhibiting Src in microglia Rhoa-deficient mice attenuates microglia dysregulation and the ensuing neurological phenotype. We also found that the Rhoa\/Src signaling pathway was disrupted in microglia of the APP\/PS1 mouse model of Alzheimer\u2019s disease and that low doses of A\u00df oligomers triggered microglia neurotoxic polarization through the disruption of Rhoa-to-Src signaling. Overall, our results indicate that disturbing RhoGTPase signaling in microglia can directly cause neurodegeneration.<\/jats:p>","DOI":"10.1101\/218107","type":"posted-content","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T10:22:18Z","timestamp":1510654938000},"source":"Crossref","is-referenced-by-count":3,"title":["Microglia dysfunction caused by the loss of Rhoa disrupts neuronal physiology and leads to neurodegeneration"],"prefix":"10.64898","author":[{"given":"Renato","family":"Socodato","sequence":"first","affiliation":[]},{"given":"Camila C.","family":"Portugal","sequence":"additional","affiliation":[]},{"given":"Teresa","family":"Canedo","sequence":"additional","affiliation":[]},{"given":"Artur","family":"Rodrigues","sequence":"additional","affiliation":[]},{"given":"Tiago O.","family":"Almeida","sequence":"additional","affiliation":[]},{"given":"Joana F.","family":"Henriques","sequence":"additional","affiliation":[]},{"given":"Sandra 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