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首页> 外文期刊>Neuron >Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer’s Disease
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Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer’s Disease

机译:Tau蛋白在阿尔茨海默病中扰乱了核细胞骨质转运

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Tau is the major constituent of neurofibrillary tangles in Alzheimer’s disease (AD), but the mechanism underlying tau-associated neural damage remains unclear. Here, we show that tau can directly interact with nucleoporins of the nuclear pore complex (NPC) and affect their structural and functional integrity. Pathological tau impairs nuclear import and export in tau-overexpressing transgenic mice and in human AD brain tissue. Furthermore, the nucleoporin Nup98 accumulates in the cell bodies of some tangle-bearing neurons and can facilitate tau aggregationin?vitro. These data support the hypothesis that tau can directly interact with NPC components, leading to their mislocalization and consequent disruption of NPC function. This raises the possibility that NPC dysfunction contributes to tau-induced neurotoxicity in AD and tauopathies.
机译:TAU是阿尔茨海默病(AD)中神经纤维缠结的主要组成部分,但是底层相关神经损伤的机制尚不清楚。 在这里,我们表明Tau可以与核孔隙络合物(NPC)的核锁素直接相互作用,并影响其结构和功能完整性。 病理Tau损害Tau过度表达转基因小鼠和人类广告脑组织的核进出口。 此外,核常素NUP98积聚在一些缠绕的神经元的细胞体中,并且可以促进Tau aggregationin?体外。 这些数据支持Tau可以直接与NPC组件进行互动的假设,导致它们的错误分析和随后对NPC功能的破坏。 这提出了NPC功能障碍有助于陶氏菌诱导的广告和介透氧化物的可能性。

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