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Insulin\u2010like growth factor\u2010I (IGF\u2010I) is synthesized in the liver and fibroblasts, and its biological actions are mediated by the IGF\u2010I receptor (IGF\u2010IR). The binding of IGF\u2010I to IGF\u2010IR leads to the activation of phosphatidylinositol 3\u2010kinase (PI3K). Activated PI3K stimulates the production of phosphatidylinositol (4,5)\u2010bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5)\u2010trisphosphate [PI(3,4,5)P3]. The PH domain of AKT (protein kinase B, PKB) (v\u2010AKT murine thymoma viral oncogene homolog) binds to PI(4,5)P2 and PI(3,4,5)P3, followed by phosphorylation of the Thr308 and Ser473 regulatory sites. Tuberous sclerosis complex 1 (TSC1) and TSC2 are upstream regulators of mammalian target of rapamycin (mTOR) and downstream effectors of the PI3K\/AKT signaling pathway. The activation of AKT suppresses the TSC1\/TSC2 heterodimer, which is an upstream regulator of mTOR. Dysregulated IGF\u2010I\/PI3K\/AKT\/mTOR signaling has been shown to be associated with autism spectrum disorders (ASDs). In this review, we discuss the emerging evidence for a functional relationship between the IGF\u2010I\/PI3K\/AKT\/mTOR pathway and ASDs, as well as a possible role of this signaling pathway in the diagnosis and treatment of ASDs.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2014.03.006","type":"journal-article","created":{"date-parts":[[2014,3,22]],"date-time":"2014-03-22T22:58:59Z","timestamp":1395529139000},"page":"35-41","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":145,"title":["Dysregulation of the IGF\u2010I\/PI3K\/AKT\/mTOR signaling pathway in autism spectrum disorders"],"prefix":"10.1002","volume":"35","author":[{"given":"Jianling","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Psychotic Disorders Shanghai Mental Health Center Shanghai Jiao Tong University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Alberts","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences, LaGuardia CC City University of New York New York NY 11101 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Li","sequence":"additional","affiliation":[{"name":"New York State Institute for Basic Research in Developmental Disabilities New York 10301 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,3,21]]},"reference":[{"issue":"6","key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"e67149","DOI":"10.1371\/journal.pone.0067149","article-title":"Functional role of mTORC2 versus integrin\u2010linked kinase in mediating Ser473\u2010Akt phosphorylation in PTEN\u2010negative prostate and breast cancer cell lines","volume":"8","author":"Agoulnik I.U.","year":"2013","journal-title":"PLoS ONE"},{"issue":"23","key":"e_1_2_7_3_1","doi-asserted-by":"crossref","first-page":"6541","DOI":"10.1002\/j.1460-2075.1996.tb01045.x","article-title":"Mechanism of activation of protein kinase B by insulin and IGF\u20101","volume":"15","author":"Alessi D.R.","year":"1996","journal-title":"EMBO J."},{"issue":"2","key":"e_1_2_7_4_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/13810","article-title":"Rett syndrome is caused by mutations in X\u2010linked MECP2, encoding methyl\u2010CpG\u2010binding protein 2","volume":"23","author":"Amir R.E.","year":"1999","journal-title":"Nat. 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