Expression of mutant ubiquitin and proteostasis impairment in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex brains
Expression of mutant ubiquitin and proteostasis impairment in Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex brains
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Kii 肌萎缩侧索硬化症/帕金森病-痴呆症复合体脑中突变泛素的表达和蛋白质稳态损伤
DOI：
10.1093/jnen/nlaa056
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Fred W. van Leeuwen
中科院分区：
文献类型：
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作者：
Bert M. Verheijen;Satoru Morimoto;Ryogen Sasaki;Kiyomitsu Oyanagi; Yasumasa Kokubo;Shigeki Kuzuhara; Fred W. van Leeuwen
纪井肌萎缩性侧索硬化症/帕金森-痴呆复合体（ALS/PDC）是日本纪井半岛特有的一种进行性神经退行性疾病。该疾病的临床特征是帕金森病、痴呆和运动神经元症状的可变组合。尽管进行了广泛的研究，但ALS/PDC的病因和发病机制仍不清楚。在神经病理水平上，Kii ALS/PDC以神经元丢失和tau显性多蛋白病为特征。在这里，我们报道了一些Kii ALS/PDC病例（n = 4）的死后脑组织中涉及蛋白质稳态途径的几种蛋白质的积累，即泛素-蛋白酶体系统和自噬-溶酶体途径。特别令人感兴趣的是泛素蛋白突变体（UBB+1）的存在，这表明泛素稳态被破坏。研究结果表明，在Kii ALS/PDC中，蛋白质异常聚集与蛋白质稳态通路受损有关。
Kii amyotrophic lateral sclerosis/parkinsonism-dementia complex (ALS/PDC) is a progressive neurodegenerative disorder that is endemic to the Kii peninsula of Japan. The disorder is clinically characterized by a variable combination of parkinsonism, dementia, and motor neuron symptoms. Despite extensive investigations, the etiology and pathogenesis of ALS/PDC remain unclear. At the neuropathological level, Kii ALS/PDC is characterized by neuronal loss and tau-dominant polyproteinopathy. Here, we report the accumulation of several proteins involved in protein homeostasis pathways, that is, the ubiquitin-proteasome system and the autophagy-lysosome pathway, in postmortem brain tissue from a number of Kii ALS/PDC cases (n = 4). Of particular interest is the presence of a mutant ubiquitin protein (UBB+1), which is indicative of disrupted ubiquitin homeostasis. The findings suggest that abnormal protein aggregation is linked to impaired protein homeostasis pathways in Kii ALS/PDC.