Neurodegenerative polyglutamine (polyQ) disorders are caused by trinucleotide repeat expansions within the coding region of disease-causing genes. PolyQ-expanded proteins undergo conformational changes leading to the formation of protein inclusions which are associated with selective neuronal degeneration. Several lines of evidence indicate that these mutant proteins are associated with oxidative stress, proteasome impairment and microglia activation. These events may correlate with the induction of inflammation in the nervous system and disease progression. Here, we review the effect of polyQ-induced oxidative stress in cellular and animal models of polyQ diseases. Furthermore, we discuss the interplay between oxidative stress, neurodegeneration and neuroinflammation using as an example the well-known neuroinflammatory disease, Multiple Sclerosis. Finally, we review some of the pharmaceutical interventions which may delay the onset and progression of polyQ disorders by targeting disease-associated mechanisms.

中文翻译：

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氧化应激和神经变性：PolyQ 疾病中的相互关联过程

神经退行性聚谷氨酰胺 (polyQ) 疾病是由致病基因编码区内的三核苷酸重复扩增引起的。PolyQ 扩增的蛋白质发生构象变化，导致形成与选择性神经元变性相关的蛋白质内含物。若干证据表明，这些突变蛋白与氧化应激、蛋白酶体损伤和小胶质细胞活化有关。这些事件可能与神经系统炎症的诱导和疾病进展相关。在这里，我们回顾了 polyQ 诱导的氧化应激在 polyQ 疾病的细胞和动物模型中的影响。此外，我们以众所周知的神经炎性疾病多发性硬化症为例，讨论氧化应激、神经变性和神经炎症之间的相互作用。