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There is no efficacious medication for FXS. Through in silico screening with a public database, computational analysis of transcriptome profile in FXS mouse neurons predicts therapeutic value of an FDA-approved drug trifluoperazine. Systemic administration of low-dose trifluoperazine at 0.05\u2009mg\/kg attenuates multiple FXS- and autism-related behavioral symptoms. Moreover, computational analysis of transcriptome alteration caused by trifluoperazine suggests a new mechanism of action against PI3K (Phosphatidylinositol-4,5-bisphosphate 3-kinase) activity. Consistently, trifluoperazine suppresses PI3K activity and its down-stream targets Akt (protein kinase B) and S6K1 (S6 kinase 1) in neurons. Further, trifluoperazine normalizes the aberrantly elevated activity of Akt and S6K1 and enhanced protein synthesis in FXS mouse. Together, our data demonstrate a promising value of transcriptome-based computation in identification of therapeutic strategy and repurposing drugs for neurological disorders, and suggest trifluoperazine as a potential treatment for FXS.<\/jats:p>","DOI":"10.1038\/s42003-020-0833-4","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T07:05:42Z","timestamp":1584342342000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Transcriptome signature analysis repurposes trifluoperazine for the treatment of fragile X syndrome in mouse model"],"prefix":"10.1038","volume":"3","author":[{"given":"Qi","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferzin","family":"Sethna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Ting","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"833_CR1","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1146\/annurev-pathol-011811-132457","volume":"7","author":"MR Santoro","year":"2012","unstructured":"Santoro, M. 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