Role of NUB1 in inclusion body formation in neurodegenerative disorders

最近，我们发现，在帕金森病(PD)和路易体痴呆(DLB)中，NUB1是一种与突触素-1相互作用的蛋白，在多系统萎缩(MSA)中，NUB1和突触素-1都积聚在路易小体和神经胶质细胞胞浆内。在这项研究中，进一步研究了NUB1在各种神经退行性疾病中的免疫组织化学定位。在对照组中，抗NUB1抗体对神经元核膜进行了弱免疫标记。在PD和DLB中，皮质和脑干型路易体、苍白体和路易氏突起均被抗NUB1强阳性标记。在MSA中，神经元和少突胶质细胞的胞浆内包涵体、神经元核包涵体和肿胀的轴突内均有NUB1免疫反应阳性。在其他疾病中，包括阿尔茨海默病、匹克病、进行性核上性麻痹、皮质基底膜变性…在内的各种其他神经元或神经胶质包涵体中未发现NUB1免疫反应运动神经元病和三联体重复病。这些发现表明，根瘤的异常堆积！接下来，我们对25例有不同程度路易小体病理的有症状和症状前帕金森病患者的新纹状体进行了免疫组织化学检测，使用抗磷酸化的α-突触核蛋白(α-synuclein，αS)抗体。这些患者根据Braak等人提出的PD分期进行分类。αS免疫组织化学显示新纹状体内有神经元和胶质细胞胞浆内包涵体及神经元性改变。αS包涵体见于中型神经元(向苍白球投射的GABA能神经元)和大型神经元(胆碱能中间神经元)，前者在第III期开始出现，后者在第V期和第VI期开始出现。神经元和胶质包涵体也在第III期开始出现。神经元和神经胶质包涵体的数量和程度与PD分期有关(p&lt；0.001)。这些发现表明，在帕金森病进展过程中，固有的新纹状体神经元通过αS聚集而退化。较少

Recently, we showed that NUB1 is a synphilin-1-interacting protein and that NUB1, as well as synphilin-1, accumulates in Lewy bodies in Parkinson's disease (PD) and dementia with Lewy bodies (DLB), and glial cytoplasmic inclusions in multiple system atrophy (MSA). In this study, an investigation was further conducted to elucidate the immunohistochemical localization of NUB1 in various neurodegenerative disorders. In controls, anti-NUB1 antibody weakly immunolabeled the neuronal perikarya. In PD and DLB, cortical and brainstem-type Lewy bodies, pale bodies and Lewy neurites were strongly immunolabeled with anti-NUB1. In MSA, NUB1 immunoreactivity was found in the intracytoplasmic inclusions of both neuronal and oligodendroglial cells, neuronal nuclear inclusions, and swollen neurites. No NUB1 immunoreactivity was found in a variety of other neuronal or glial inclusions in other disorders, including Alzheimer's disease, Pick's disease, progressive supranuclear palsy, corticobasal degener … More ation, motor neuron disease and triplet-repeat diseases. These findings indicate that the abnormal accumulation of NUB! is specific for α-synucleinopathy lesions.Next, we immunohistochemically examined the neostriatum from 25 patients with symptomatic and presymptomatic PD with various degrees of Lewy body pathology, using anti-phosphorylated α-synuclein (αS) antibody. These patients were classified, according to the PD staging proposed by Braak et al. αS immunohistochemistry revealed neuronal and glial cytoplasmic inclusions and neuritic changes in the neostriatum. αS inclusions were found in the medium-sized neurons (GABAergic neurons that project to the globus pallidus) and large neurons (cholinergic interneurons); the former began to appear at stage III and the latter was noted at stages V and VI. Neuritic changes and glial inclusions also began to appear at stage III. The numbers of neuronal and glial inclusions and the extent of neuritic changes correlated with the PD stage (p<0.001). These findings-suggest that intrinsic neostriatal neurons degenerate through αS aggregation during PD progression. Less