Tuberous sclerosis complex (TSC) results from loss of a tumor suppressor gene - TSC 1 or TSC 2, encoding hamartin and tuberin, respectively. These proteins formed a complex to inhibit mTORC1-mediated cell growth and proliferation. Loss of either protein leads to overgrowth lesions in many vital organs.

2017年12月1日 · Phosphorylated ribosomal protein S6 (pS6) is a commonly used marker for mTOR hyperactivation. In this study, immunohistochemical analysis was used to examine the presence of pS6 in the brains of 7 dpf WT, tsc2 +/− and tsc2 −/− larvae.

2016年11月18日 · Loss of either TSC1 or TSC2 gene function abolishes Rheb-GTPase activity, resulting in constitutively activated mTORC1 kinase and consequently increased levels of the S6 ribosomal protein ...

2004年10月13日 · Approximately 80% of the Tsc2 −/− MEFs expressing exogenous tuberin and approximately 60% of the Tsc1 −/− MEFs expressing exogenous hamartin had no detectable phosphorylated S6 (pS6 ...

2011年11月4日 · Mutant SVZ showed significant reduction in both Tsc1 and Tsc2 proteins, with no activation in pS6 or difference in pERK or pAkt (Figure 5E). Whereas accumulation of Type A neuroblasts could be detected dorsally, alterations in Type B SC distribution were observed along the entire wall of the SVZ ( Figure 5 F).

(A) pS6 expression in Tsc2 hypomorphic mice (KC+) is three times higher than in CC− littermate controls, indicating a strong mTORC1 upregulation. (B) KC+ mice treated with TC1 (3 mg/kg) show a significant reduction of pS6 levels at 3‐h postadministration.

2022年12月1日 · In this study, we generated a novel mouse model involving conditional deletion of Tsc1 in lysozyme 2 (Lyz2)-positive cells which replicated several features of brain lesions including epileptic seizures, megalencephaly, highly …

In this study, we generated a novel mouse model involving conditional deletion of Tsc1 in lysozyme 2 (Lyz2)-positive cells which replicated several features of brain lesions including epileptic seizures, megalencephaly, highly enlarged pS6-positive neurons and astrogliosis.

Dysplastic neurons, giant cells, and dysplastic astroglia express high levels of pS6 and demonstrate altered GluR subunit composition, resembling those of normal immature neurons and glia. In contrast, nondysplastic neurons in TSC and non-TSC epileptic lesions express lower pS6 levels and display changes in GluR subunit expression that are ...

Surgically resected human cortical tubers and nondysplastic epileptic cortical samples were analyzed by double-label immunocytochemistry for coexpression of neuronal and glial markers, the TSC1/TSC2 pathway downstream molecule phospho-S6 (pS6) and GluR subunits, and compared with control cortical tissue.