کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4337802 | 1614824 | 2013 | 15 صفحه PDF | دانلود رایگان |
• Focal malformations of cortical development (FMCD) are a cause of epilepsy.
• FMCD are associated with enhanced activation of mTOR signaling.
• FMCD are often caused by germline or somatic mutations in mTOR pathway genes.
• Epilepsy in FMCD may be treated with mTOR inhibitors.
Focal malformations of cortical development (FMCD) are highly associated with several neurological disorders including intractable epilepsy and neurocognitive disabilities. Over the past decade, several FMCD subtypes have been linked to hyperactivation of the mammalian target of rapamycin (mTOR) signaling cascade. In view of the roles that mTOR plays in cell proliferation, size, motility, and stem cell phenotype, many of the features of FMCD such as cytomegaly, disorganized lamination, and expression of stem cell markers can be explained by enhanced mTOR signaling. FMCD result from several distinct and fascinating molecular mechanisms including biallelic gene inactivation, somatic mutation, and potentially, viral infection. These mechanisms have been directly linked to mTOR activation. Perhaps most compelling, pharmacological inhibition of mTOR has been implemented successfully in clinical trials for select FMCD and provides a new vista for treatment.
Journal: Neuroscience - Volume 252, 12 November 2013, Pages 262–276