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TSC by evaluating the coding and non-coding transcriptional landscape of TSC cortical tubers using mRNA and small RNA sequencing. We examined the functional properties of the miR34 family, which was upregulated in TSC tubers, and found that miR34b was involved in the regulation of neurite outgrowth in neurons.
In chapter 4, we evaluated a possible relationship between the expression the proteasome, a multisubunit enzyme complex involved in protein degradation, and the clinical course of epilepsy in MCD. We investigated the expression and cellular distribu- tion of both constitutive (β1, β5) and immunoproteasome (β1i, β5i) subunits in surgically resected brain material and in cell cultures derived from patients with FCD type II or TSC.
miRNAs miR21, miR146a and miR155 were previously shown to be differentially expressed in human epileptogenic brain and in experimental models of epilepsy. In chap- ter 5, we aimed to evaluate the expression of these three miRNAs in TSC cortical tubers and to determine their functional role in inflammation in human astrocytes and in cell cultures from TSC patient-derived subependymal giant cell astrocytomas.
In chapter 6, we aimed at identifying potential new miRNAs that are involved in IL-1β-mediated inflammation in human astrocytes, using small RNA sequencing of stim- ulated fetal astrocyte cultures. We identified a novel key regulator of IL-1β-mediated inflammation in astrocytes cultures, miR147b, of which we also examined several func- tional characteristics in relation to inflammation-related cellular processes.
In chapter 7, the content of this thesis is discussed, supplemented with prelim- inary data of ongoing research, and some promising future perspectives are suggested.