| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2015: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Outline of Final Research Achievements |
We performed whole exome sequencing using paired samples from Sturge Weber syndrome and FCD Type IIb subjects and further investigated using deep sequencing. We identified lesion-specific somatic GNAQ mutation in individuals with Sturge Weber syndrome and MTOR mutations in individuals with FCD Type IIb. Functional analyses showed that phosphorylation of ribosomal protein S6 in FCD Type IIb brain tissues with MTOR mutations was clearly elevated compared with control samples. Transfection of any of the four MTOR mutants into HEK293T cells led to elevated phosphorylation of 4EBP, the direct target of mTOR kinase. These findings suggest that mutations in MTOR are likely to cause hyperactivation of the mTOR signaling pathway and induce dysregulation of growth of neurons and glia, or presumably of their progenitors during brain development. MTOR mutations are sensitive to rapamycin, therefore, mTOR inhibitors would be able to alleviate intractable epilepsy caused by MTOR mutations.
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