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首页> 外文期刊>Neurobiology of disease >Brain region- and age-dependent dysregulation of p62 and NBR1 in a mouse model of Huntington's disease
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Brain region- and age-dependent dysregulation of p62 and NBR1 in a mouse model of Huntington's disease

机译：亨廷顿舞蹈症小鼠模型中p62和NBR1的大脑区域和年龄依赖性失调

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Huntington's disease is characterized by the formation of protein aggregates, which can be degraded by macroautophagy. Here, we studied protein levels and intracellular distribution of p62 and NBR1, two macroautophagy cargo receptors, during disease progression. In R6/1 mice, p62 and NBR1 protein levels were decreased in all brain regions analyzed early in the disease, whereas at late stages they accumulated in the striatum and hippocampus, but not in the cortex. The accumulation of p62, but not NBR1, occurred in neuronal nuclei, where it co-localized with mutant huntingtin inclusions, both in R6/1 and Huntington's disease patients. Moreover, exportin-1 was selectively decreased in old R6/1 mice brain, and could worsen p62 nuclear accumulation. In conclusion, p62 interacts with mutant huntingtin and is retained in the nucleus along the progression of the disease, mostly in striatal and hippocampal neurons. Thus, cytoplasmic NBR1 might be important to maintain basal levels of selective macroautophagy in these neurons. ? 2012 Elsevier Inc.
机译：亨廷顿舞蹈病的特征是蛋白质聚集体的形成，可被巨噬细胞自噬降解。在这里，我们研究了疾病发展过程中两个大自噬货物受体p62和NBR1的蛋白质水平和细胞内分布。在R6 / 1小鼠中，在疾病早期分析的所有脑区域中，p62和NBR1蛋白水平均降低，而在晚期，它们在纹状体和海马中蓄积，但不在皮质中蓄积。在R6 / 1和亨廷顿舞蹈病患者中，p62的积累而不是NBR1发生在神经元核中，并与突变的亨廷顿蛋白包涵体共定位。此外，出口蛋白-1在老R6 / 1小鼠脑中选择性降低，并可能加剧p62核积累。总之，p62与亨廷顿蛋白突变体相互作用，并沿疾病进展保留在细胞核中，主要存在于纹状体和海马神经元中。因此，胞质NBR1可能对于维持这些神经元中选择性巨噬自噬的基础水平很重要。 ？ 2012爱思唯尔公司

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