A fine balance between Prpf19 and Exoc7 in achieving degradation of aggregated protein and suppression of cell death in spinocerebellar ataxia type 3

Chen, ZS; Huang, X; Talbot, K; Chan, HYE

Journal article

A fine balance between Prpf19 and Exoc7 in achieving degradation of aggregated protein and suppression of cell death in spinocerebellar ataxia type 3

Abstract:: Spinocerebellar Ataxia Type 3 (SCA3) is a member of the family of polyglutamine (polyQ) neurodegenerative disorders that includes Huntington\u27s Disease and several other SCAs. SCA3, the most common dominant ataxia in the world, is caused by polyQ tract expansion in the protein, ataxin-3. How SCA3 occurs and how to treat it remain unresolved issues. The primary culprit of toxicity in all polyQ diseases is the glutamine repeat: its abnormal expansion leads to neuronal dysfunction and death. With that said, there is indisputable evidence that the way polyQ-dependent toxicity presents—areas impacted, cellular processes perturbed—is predicated in large part on regions outside of the polyQ tract, i.e., protein context. Defining the role of non-polyQ regions of ataxin-3 in the toxicity of its expanded glutamine tract will increase our understanding of the biology of disease in SCA3. Functions including ubiquitin binding, proteasome shuttling, and aggregation depend heavily on these non-polyQ regions. The work highlighted in this dissertation expands on the current understanding of protein context in SCA3 by providing a detailed investigation into the importance of various ataxin-3 domains and interactions to disease pathogenesis. It leans on the genetic versatility of the Drosophila melanogaster model organism to develop novel methods of studying the ataxin-3 interactome and its impact on polyQ expanded ataxin-3 toxicity. All this in hopes that it will help uncover potential therapeutic targets for this currently incurable disorder

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Chen, Z. S., Huang, X., Talbot, K., & Chan, H. Y. E. (2021). A fine balance between Prpf19 and Exoc7 in achieving degradation of aggregated protein and suppression of cell death in spinocerebellar ataxia type 3. Cell Death & Disease, 12(2), 136–136.

MLA Style

Chen, ZS, et al. “A Fine Balance between Prpf19 and Exoc7 in Achieving Degradation of Aggregated Protein and Suppression of Cell Death in Spinocerebellar Ataxia Type 3.” Cell Death & Disease, vol. 12, no. 2, 2021, pp. 136–36.

Chicago Style

Chen, ZS, X Huang, K Talbot, and HYE Chan. 2021. “A Fine Balance between Prpf19 and Exoc7 in Achieving Degradation of Aggregated Protein and Suppression of Cell Death in Spinocerebellar Ataxia Type 3.” Cell Death & Disease 12 (2): 136–36.
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