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conditions in vitro. In chapter 6, using next generation sequencing we identified miR147b as a novel key regulator of IL-1β-mediated inflammation in human astrocytes cultures.
We also found that both miR146a and miR147b were able to restore aberrant astrocytic proliferation and promote neuronal differentiation of neuronal stem cells, and therefore these miRNAs deserve further investigation as potential therapeutic therapy in neuro- logical disorders associated with inflammation, such as epilepsy.
We were able to correlate several aspects of the transcriptional landscape of TSC tubers to our histological definition of the different tuber types, which is described in chapter 7. Additionally, we presented novel preliminary data indicating that the grey matter in TSC tubers seems more affected compared to the white matter. We also pro- posed, using Library of Integrated Network-based Cellular Signatures (LINCS) analysis of the transcriptomics data of cortical tubers compared to controls, TPCA-1 as interesting compound for restoring the altered gene expression in TSC.
Taken together, we found that inflammatory pathways are amongst the main deregulated systems in TSC tubers and therefore represent excellent targets for fur- ther exploration. We identified specific deregulated biological signaling pathways and potential targets for treatment. Using astrocyte cell cultures, we determined functional characteristics of several targets that are deregulated in cortical tubers and our data suggest that miRNAs might be of therapeutic value in the treatment of drug-resistant epilepsy in TSC. Furthermore, results from pre-clinical and clinical studies are encour- aging and indicate that miRNAs may have therapeutic value in treating drug-resistant epilepsy. Therefore, the administration of miRNAs could be a promising new therapy in the treatment of epilepsy and TSC.