UBE3A ubikitina ligasaren funtzioa indargabetzen duten deubikitinasak identifikatzea eta inhibitzea Angelman sindromea tratatzeko estrategia terapeutiko gisa

Abstract

Angelman Syndrome (AS) is a rare disease that develops when the UBE3A gene is not expressed in the brain or the protein it encodes for is defective. UBE3A E3 is a ubiquitin ligase, that is, it is responsible for attaching to its targets a small protein called ubiquitin. As AS is currently a disease that has no cure, our main objective is to develop a new treatment. In order to do so, we will identify and inhibit deubiquitinase(s) (DUBs) which have an opposite function to UBE3A. To find those DUBs, we propose the following two approaches: (i) identifying the proteins that interact with UBE3A in the fly brain, and (ii) the identification of UBE3A substrates in the brain of an AS mouse model. Once candidate DUB(s) are identified, they will be inhibited in AS mice models to assess their impact on AS symptomatology.