Instituto de Biologia Molecular e Celular, Universidade do Porto , Porto , Portugal.
Front Neurol. 2013 Jun 20;4:76. doi: 10.3389/fneur.2013.00076. eCollection 2013.
Trinucleotide repeat (TNR) expansions are present in a wide range of genes involved in several neurological disorders, being directly involved in the molecular mechanisms underlying pathogenesis through modulation of gene expression and/or the function of the RNA or protein it encodes. Structural and functional information on the role of TNR sequences in RNA and protein is crucial to understand the effect of TNR expansions in neurodegeneration. Therefore, this review intends to provide to the reader a structural and functional view of TNR and encoded homopeptide expansions, with a particular emphasis on polyQ expansions and its role at inducing the self-assembly, aggregation and functional alterations of the carrier protein, which culminates in neuronal toxicity and cell death. Detail will be given to the Machado-Joseph Disease-causative and polyQ-containing protein, ataxin-3, providing clues for the impact of polyQ expansion and its flanking regions in the modulation of ataxin-3 molecular interactions, function, and aggregation.
三核苷酸重复（TNR）扩展存在于广泛涉及多种神经退行性疾病的基因中，通过调节基因表达和/或其编码的 RNA 或蛋白质的功能，直接参与发病机制的分子机制。了解 TNR 扩展在神经退行性变中的作用，需要有关 TNR 序列在 RNA 和蛋白质中的结构和功能的信息。因此，本综述旨在为读者提供 TNR 和编码同聚肽扩展的结构和功能视图，特别强调聚 Q 扩展及其诱导载体蛋白自组装、聚集和功能改变的作用，最终导致神经元毒性和细胞死亡。将详细介绍导致 Machado-Joseph 疾病的蛋白和含有聚 Q 的蛋白 ataxin-3，为聚 Q 扩展及其侧翼区域在调节 ataxin-3 分子相互作用、功能和聚集中的作用提供线索。
