{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T11:12:30Z","timestamp":1791112350526,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,9,28]],"date-time":"2004-09-28T00:00:00Z","timestamp":1096329600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2004,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To evaluate the possible roles of the Akt\/PKB\u2010mTOR\u2010p70S6K\u2010S6 and cap\u2010dependent translation (eIF4G) pathways in the pathogenesis of tuberous sclerosis complex (TSC)\u2013associated cortical tubers and focal cortical dysplasia (FCD), we performed qualitative and semiquantitative immunohistochemical evaluation on surgically resected corticectomy specimens to detect phosphorylated molecules as activated downstream targets of the signaling pathways. A tissue microarray paraffin block was constructed from 63 archival specimens of surgically resected TSC tubers, FCDs with balloon cells, cortical dysplasia without balloon cells, and histologically normal\u2013appearing neocortex obtained from cases with Rasmussen encephalitis, cystic\u2013gliotic encephalopathy, and temporal lobe epilepsy. Abnormal neuroglial cells were positive for phospho\u2010S6 and phospho\u2010eIF4G with various staining intensities in FCDs and TSC tubers. Both proteins were much less abundantly expressed in normal\u2010appearing neocortex. Phospho\u2010mTOR expression was observed in neurons in all groups. The expression of phospho\u2010S6 and phospho\u2010eIF4G was associated with dysplastic lesions (<jats:italic>p<\/jats:italic> &lt; 0.05), and the cytoplasmic phospho\u2010p70S6K expression was most specific for and abundant in TSC tubers and much less prominent in other groups (<jats:italic>p<\/jats:italic> &lt; 0.01). These results suggest that constitutive activation of cytoplasmic p70S6K plays a pivotal role in the pathogenesis of TSC tubers and that FCDs possess a distinct mechanism for activation of S6 and eIF4G. Ann Neurol 2004;56:510\u2013519<\/jats:p>","DOI":"10.1002\/ana.20234","type":"journal-article","created":{"date-parts":[[2004,9,29]],"date-time":"2004-09-29T07:03:10Z","timestamp":1096441390000},"page":"510-519","source":"Crossref","is-referenced-by-count":143,"title":["Insulin signaling pathways in cortical dysplasia and TSC\u2010tubers: Tissue microarray analysis"],"prefix":"10.1002","volume":"56","author":[{"given":"Hajime","family":"Miyata","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander C. 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