α-internexin is present in the pathological inclusions of neuronal intermediate filament inclusion disease
α-internexin is present in the pathological inclusions of neuronal intermediate filament inclusion disease
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DOI：
10.1016/s0002-9440(10)63773-x
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发表时间：
2004-06-01
影响因子：
6
通讯作者：
Trojanowski, JQ
中科院分区：
文献类型：
--
作者：
Cairns, NJ;Zhukareva, V;Trojanowski, JQ
神经元中间丝包涵体病（Neuronal intermediate filament inclusion disease，NIFID）是一种早期发病的神经系统疾病，临床表现多样，包括额颞叶痴呆、锥体和锥体外系体征。在病理学上，在受影响的区域中，存在神经元损失、星形细胞增多和不含tau或α-突触核蛋白的异常神经元U的神经元胞质内聚集体。因此，为了表征NIFID中包涵体的神经元IF蛋白谱，使用一组抗神经元IF蛋白对10例NIFID、4例正常老年对照（NL）和2例阿尔茨海默病（AD）进行免疫组织化学（IHC）。对选定的病例进行免疫电子显微镜检查，并将4例额叶的冷冻组织用于生物化学研究，包括连续提取和Western印迹。基于这些研究，我们在这里首次报告了NIFID内含物中存在神经元117蛋白质α-internexin，以及所有三种神经丝亚基：重、中和轻。因此，所有IV类神经元IF蛋白都存在于这种疾病的病理性包涵体中。生物化学显示，W聚集体可溶于十二烷基硫酸钠（SDS）和没有翻译后修饰时，检测到阿尔茨海默氏症或老年对照组的大脑。因此，我们得出结论，NIFID的特点是病理性细胞质聚集的所有IV类神经元IF蛋白在大脑中。α-interexin在细胞质内含物中的发现暗示了NIFID和其他具有IF病理性积累的神经系统疾病的发病机制。
Neuronal intermediate filament (IF) inclusion disease (NIFID) is a novel neurological disease of early onset with a variable clinical phenotype including frontotemporal dementia, pyramidal, and extrapyramidal signs. Pathologically, in affected areas, there is neuronal loss, astrocytosis, and neuronal intracytoplasmic aggregates of abnormal neuronal Us that contain neither tau nor a-synuclein. Thus, to characterize the neuronal IF protein profile of inclusions in NIFID, immunohistochemistry (IHC) was performed on 10 cases of NIFID, four normal aged controls (NL), and two cases of Alzheimer's disease (AD) using a panel of anti-neuronal IF proteins. immunoelectron microscopy was performed on selected cases and frozen tissue from the frontal lobe of four cases was used for biochemical studies including sequential extractions and Western blotting. Based on these studies, we report here for the first time that alpha-internexin, a neuronal 117 protein, is present within the inclusions of NIFID as are all three neurofilament subunits: heavy, medium, and light. Thus, all class IV neuronal IF proteins are present within the pathological inclusions of this disease. Biochemistry revealed that W aggregates were soluble in sodium dodecyl sulfate (SDS) and no post-translational modification was detected when compared with Alzheimer's disease or aged control brains. Hence, we conclude that NIFID is characterized by the pathological cytoplasmic aggregation of all class IV neuronal IF proteins in brain. The discovery of alpha-internexin in the cytoplasmic inclusions implicates novel mechanisms of pathogenesis in NIFID and other neurological diseases with pathological accumulations of IFs.