State Key Laboratory of Medical Neurobiology, Neurology Department at Huashan Hospital, School of Life Sciences, Fudan University, Shanghai, China.
Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Nat Chem Biol. 2017 Nov;13(11):1152-1154. doi: 10.1038/nchembio.2461. Epub 2017 Sep 4.
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.
蛋白质错误折叠是包括亨廷顿病（HD）在内的神经退行性疾病的一个常见主题。导致 HD 的突变 huntingtin 蛋白（mHTT）具有扩展的多聚谷氨酰胺（polyQ）延伸，可能采用多种构象，其中最具毒性的是被抗体 3B5H10 识别的构象。在这里，我们表明由于其在人细胞和脑中对选择性自噬的抗性，被 3B5H10 识别的 mHTT 物种的降解速度较慢，从而揭示了其更高毒性的机制。
