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首页> 外文期刊>Neuropathology and applied neurobiology >Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in Alzheimer's disease brains
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Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in Alzheimer's disease brains

机译:Ubiquilin-1免疫反应性集中在阿尔茨海默氏病大脑中的平野体和营养不良的神经突上

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Aims: Ubiquilin-1 acts as an adaptor protein that mediates the translocation of polyubiquitinated proteins to the proteasome for degradation. Although previous studies suggested a key role of ubiquilin-1 in the pathogenesis of Alzheimer's disease (AD), a direct relationship between ubiquilin-1 and Hirano bodies in AD brains remains unknown. Methods: By immunohistochemistry, we studied ubiquilin-1 and ubiquilin-2 expression in the frontal cortex and the hippocampus of six AD and 13 control cases. Results: Numerous Hirano bodies, accumulated in the hippocampal CA1 region of AD brains, expressed intense immunoreactivity for ubiquilin-1. They were much less frequently found in control brains. However, Hirano bodies did not express a panel of markers for proteasome, autophagosome or pathogenic proteins, such as ubiquilin-2, ubiquitin, p62, LC3, beclin-1, HDAC6, paired helical filament (PHF)-tau, protein-disulphide isomerase (PDI) and phosphorylated TDP-43, but some of them expressed C9orf72. Ubiquilin-1-immunoreactive deposits were classified into four distinct morphologies, such as rod-shaped structures characteristic of Hirano bodies, dystrophic neurites contacting senile plaques, fragmented structures accumulated in the lesions affected with severe neuronal loss, and thread-shaped structures located mainly in the molecular layer of the hippocampus. Conclusions: Ubiquilin-1 immunoreactivity is concentrated on Hirano bodies and dystrophic neurites in AD brains, suggesting that aberrant expression of ubiquilin-1 serves as one of pathological hallmarks of AD.
机译:目的:Ubiquilin-1充当衔接蛋白,介导多泛素化蛋白向蛋白酶体的转运以进行降解。尽管以前的研究表明ubiquilin-1在阿尔茨海默氏病(AD)的发病机理中具有关键作用,但是ubiquilin-1和AD大脑中的Hirano体之间的直接关系仍然未知。方法:通过免疫组织化学,我们研究了6例AD和13例对照组的额叶皮层和海马中ubiquilin-1和ubiquilin-2的表达。结果:在AD脑海马CA1区积聚的许多平野小体对ubiquilin-1表现出强烈的免疫反应性。在对照大脑中发现它们的频率要低得多。但是,平野体未表达一组蛋白酶体,自噬体或致病蛋白的标记物,例如泛醇2,泛素,p62,LC3,beclin-1,HDAC6,成对的螺旋丝(PHF)-tau,蛋白-二硫键异构酶(PDI)和磷酸化的TDP-43,但其中一些表达了C9orf72。 Ubiquilin-1免疫反应性沉积物分为四个不同的形态,例如平野体的杆状结构,接触老年斑的营养不良性神经突,在受严重神经元丢失影响的病灶中积累的碎片状结构以及主要位于神经元中的线状结构。海马的分子层。结论:Ubiquilin-1的免疫反应主要集中在AD大脑的平野组织和营养不良的神经突上,提示ubiquilin-1的异常表达是AD的病理特征之一。

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