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Polyglutamine disease proteins: Commonalities and differences in interaction profiles and pathological effects

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Item Type:Review
Title:Polyglutamine disease proteins: Commonalities and differences in interaction profiles and pathological effects
Creators Name:Bonsor, M. and Ammar, O. and Schnoegl, S. and Wanker, E.E. and Silva Ramos, E.
Abstract:Currently, nine polyglutamine (polyQ) expansion diseases are known. They include spinocerebellar ataxias (SCA1, 2, 3, 6, 7, 17), spinal and bulbar muscular atrophy (SBMA), dentatorubral-pallidoluysian atrophy (DRPLA), and Huntington's disease (HD). At the root of these neurodegenerative diseases are trinucleotide repeat mutations in coding regions of different genes, which lead to the production of proteins with elongated polyQ tracts. While the causative proteins differ in structure and molecular mass, the expanded polyQ domains drive pathogenesis in all these diseases. PolyQ tracts mediate the association of proteins leading to the formation of protein complexes involved in gene expression regulation, RNA processing, membrane trafficking, and signal transduction. In this review, we discuss commonalities and differences among the nine polyQ proteins focusing on their structure and function as well as the pathological features of the respective diseases. We present insights from AlphaFold-predicted structural models and discuss the biological roles of polyQ-containing proteins. Lastly, we explore reported protein-protein interaction networks to highlight shared protein interactions and their potential relevance in disease development.
Keywords:Interactome, PolyQ Disease, PolyQ Expansion, Protein Networks, Protein Structure
Page Range:e2300114
Date:14 April 2024
Official Publication:https://doi.org/10.1002/pmic.202300114
PubMed:View item in PubMed

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