Loche, Alberto. Epigenetic and transcriptional regulation of neural development : Scml2 and Ezh2, new functions in health and disease. 2015, PhD Thesis, University of Basel, Faculty of Science.
Restricted to Repository staff only until May 2018.
Official URL: http://edoc.unibas.ch/diss/DissB_11714
Epilepsy represents one of the most prevalent and detrimental neurological diseases, characterized by a disregulation of neuronal activity resulting into unpredictable synchronized waves, or seizures, spreading throughout the central nervous system. Evidences from both animal models and from human brain tissue have started to unveil that epilepsy and epileptogenesis can be associated with epigenetic changes. Aim of this work is to describe a novel epileptic syndrome, that opens a door to a new possible mechanism at the basis of activity disregulation in the brain. SCML2 is a poorly studied gene, which translates into a member of the Polycomb Repressive Complex 1, a master regulator of gene repression and chromatin compaction. By generating mutant mice lacking the SCML2 functional protein, we discovered that its function is important to ensure proper inhibitory inputs onto excitatory neurons. A similar mechanism may be acting in the cortex as well as in the spinal cord, leading to hyperexcitability and the development of synchronous activity upon challenge. Our analysis provides the first case of a Polycomb protein involved in the pathogenesis of human epilepsy and shed some light into a possible whole new field of investigation, where a deeper understanding of such epigenetic processes will likely lead to exciting new discoveries and possible new treatment options for a highly unmet medical need.
|Advisors:||Rijli, Filippo M. and Sassone-Corsi, Paolo|
|Faculties and Departments:||09 Associated Institutions > Friedrich Miescher Institut FMI > Transcriptional mechanisms of topographic circuit formation (Rijli)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||1 Online-Ressource (108 Seiten)|
|Last Modified:||16 Sep 2016 08:07|
|Deposited On:||16 Sep 2016 08:06|
Repository Staff Only: item control page