Nörotrofin reseptörü ile ilişkili ölüm bölgesi proteininin WNT/ß- katenin sinyal iletiminin düzenlenmesindeki rolünün zebra balığı modelinde araştırılması

Wnt/β-catenin signalling pathway is crucial for developmental processes and tissue homeostasis. Abnormal regulation of this signalling transduction might lead to several disorders. Hence, the understanding mechanisms underlying Wnt-related diseases might provide benefits for novel therapeutic approaches. For this purpose, elucidation of the roles of the modulators in this pathway has a significant importance for discovering novel drug targets. In the context of this thesis, the role of the neurotrophin receptor associated death domain protein (Nradd), which is a homolog of p75 neurotrophin receptor (p75NTR), in regulation of Wnt/ß-catenin signaling was investigated using the zebrafish model. Since the Nradd is a transmembrane protein with an intracellular death domain, it is able to induce apoptosis in healthy and cancerous cells. Therefore, the relationship between regulatory role as part of the Wnt/ß-catenin signaling and induction of apoptosis in cell culture and zebrafish model has been aimed to be unravelled. As a result of this modulation mechanism, the interaction between Nradd and other Wnt components was determined as a indicator of the dual role of this novel death domain protein. Based on our biochemical and molecular biological results, Nradd was identified as a novel feedback regulator of the Wnt/β-catenin signalling pathway. Consequently, we propose that targeting Wnt signalling via modulation of Nradd in novel treatment strategies could be beneficial for eradicating neurological disorders.