Protein misfolding is a common theme in neurodegenerative disorders including Huntington's disease (HD). The HD-causing mutant huntingtin protein (mHTT) has an expanded polyglutamine (polyQ) stretch that may adopt multiple conformations, and the most toxic of these is the one recognized by antibody 3B5H10. Here we show that the 3B5H10-recognized mHTT species has a slower degradation rate due to its resistance to selective autophagy in human cells and brains, revealing mechanisms of its higher toxicity.

中文翻译：

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有毒的亨廷顿蛋白突变体对选择性自噬具有抵抗力

蛋白质错误折叠是包括亨廷顿舞蹈病（HD）在内的神经退行性疾病的常见主题。引起HD的突变型亨廷顿蛋白（mHTT）具有扩展的聚谷氨酰胺（polyQ）片段，该片段可能采用多种构象，其中最具毒性的是抗体3B5H10所识别的一种。在这里，我们显示3B5H10公认的mHTT物种具有较慢的降解速度，这是由于其对人类细胞和大脑中的选择性自噬具有抵抗力，揭示了其更高毒性的机理。