Institute of Biophysics (IBF), Trento Unit, National Research Council (CNR), Via Sommarive 18, 38123 Trento, Italy.
Biomol Concepts. 2022 Mar 31;13(1):183-199. doi: 10.1515/bmc-2022-0018.
Polyglutamine (polyQ) diseases are a family composed of nine neurodegenerative inherited disorders (NDDs) caused by pathological expansions of cytosine-adenine-guanine (CAG) trinucleotide repeats which encode a polyQ tract in the corresponding proteins. CAG polyQ repeat expansions produce neurodegeneration via multiple downstream mechanisms; among those the neuronal activity underlying the ion channels is affected directly by specific channelopathies or indirectly by secondary dysregulation. In both cases, the altered excitability underlies to gain- or loss-of-function pathological effects. Here we summarize the repertoire of ion channels in polyQ NDDs emphasizing the biophysical features of neuronal excitability and their pathogenic role. The aim of this review is to point out the value of a deeper understanding of those functional mechanisms and processes as crucial elements for the designing and targeting of novel therapeutic avenues.
多聚谷氨酰胺（polyQ）疾病是一组由九种神经退行性遗传性疾病（NDDs）组成的家族，这些疾病是由胞嘧啶-腺嘌呤-鸟嘌呤（CAG）三核苷酸重复序列的病理性扩增引起的，这些重复序列在相应的蛋白质中编码一个多聚 Q 片段。CAG 多聚 Q 重复扩增通过多种下游机制导致神经退行性变；其中，神经元活动直接受到特定通道病的影响，或间接受到二级失调的影响。在这两种情况下，改变的兴奋性是获得或丧失功能的病理性效应的基础。在这里，我们总结了多聚 Q NDDs 中的离子通道谱，强调了神经元兴奋性的生物物理特征及其致病作用。本综述的目的是指出更深入地了解这些功能机制和过程作为设计和靶向新型治疗途径的关键要素的价值。
