In-silico prediction of the complete ataxin-3 protein network relevant for Spinocerebellar Ataxia type 3 (SCA3)

Batista, Paulo Jorge Canedo

http://hdl.handle.net/10400.22/29500

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Authors

Batista, Paulo Jorge Canedo

Advisor(s)

Vieira, Cristina

Faria, Brígida Mónica

Vieira, Jorge

Abstract(s)

Spinocerebellar Ataxia Type 3 (SCA3), also known as Machado-Joseph disease, is a neurodegenerative disorder caused by an expanded (exp) polyglutamine (polyQ) tract in ataxin-3. This study aims to characterize the ataxin-3 network, using identified interactors in main databases, as well as interactors from interlogs, cell models of the disease, and/or other animal models. Furthermore, in-silico analyses, using different 3D protein structure predictions, were performed to identify interacting regions (IR), that have been used to confirm the predictions. These proteins were divided into two groups, those that bind more at JD region and those that bind more at C-terminal region. Five IR have been identified in the first group, and one for the second group, respectively. The research focused on 355 proteins described in main databases, and for 323 evidence supports them as true ataxin-3 interactors. Furthermore, 42 new proteins are also predicted as new ataxin-3 interactors. Moreover, 60 ataxin-3 interactors that behave differently in the presence of an exp polyQ region have been identified, and these may be key SCA3 factors. In conclusion, these findings contribute to a deeper understanding of SCA3 pathogenesis and offer potential targets for future experimental studies.