Phosphorylation of MAP 1A regulates hyperphosphorylation of Tau in Alzheimer's disease model.

IF 4 2区医学 Q1 CLINICAL NEUROLOGY

Neuropathology and Applied Neurobiology Pub Date : 2023-10-01 DOI:10.1111/nan.12934

Biao Cai, Nan Shao, Ting Ye, Peng Zhou, Wenwen Si, Hang Song, Guangyun Wang, Junping Kou

引用次数: 0

Abstract

Hyperphosphorylation of Tau is one of the important pathological features of Alzheimer's disease (AD). Therefore, studying the mechanisms behind Tau hyperphosphorylation is crucial in exploring the pathogenesis of neurological damage in AD.

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MAP 1A的磷酸化调节阿尔茨海默病模型中Tau的过度磷酸化。

背景与目的：Tau磷酸化过度是阿尔茨海默病（AD）的重要病理特征之一。因此，研究Tau过度磷酸化背后的机制对于探索AD神经损伤的发病机制至关重要。方法：本研究在建立AD大鼠模型后，对蛋白质进行了定量磷酸蛋白质组学和蛋白质组学鉴定，表明模型组微管相关蛋白1A（MAP 1A）的磷酸化水平较低。Western印迹证实了MAP 1A在SD大鼠、APP/PS1转基因小鼠和细胞AD模型中的变化。为了进一步研究重组MAP 1A磷酸化影响Tau磷酸化的分子机制，在AD细胞模型中进行了干扰siRNA MAP 1A和蛋白质免疫沉淀反应分析。结果：细胞周期蛋白依赖性激酶5（CDK5）与MAP 1A的结合减少，与Tau的结合增加，导致磷酸化MAP 1A（p-MAP 1A）减少，磷酸化Tau（p-Tau）增加，MAP 1A沉默促进CDK5-Tau的结合，增加Tau磷酸化，从而降低细胞存活率。结论：总之，我们发现p-MAP 1A的下调与p-Tau的上调相关，是由于它们与CDK5的结合力改变，并且MAP 1A可以通过竞争性结合CDK5来增强自身磷酸化，并拮抗Tau磷酸化。这导致AD中的神经元保护和降低组织损伤水平，有助于更好地了解AD的发病机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuropathology and Applied Neurobiology 医学-病理学

CiteScore

8.20

自引率

2.00%

发文量

审稿时长

6-12 weeks

期刊介绍： Neuropathology and Applied Neurobiology is an international journal for the publication of original papers, both clinical and experimental, on problems and pathological processes in neuropathology and muscle disease. Established in 1974, this reputable and well respected journal is an international journal sponsored by the British Neuropathological Society, one of the world leading societies for Neuropathology, pioneering research and scientific endeavour with a global membership base. Additionally members of the British Neuropathological Society get 50% off the cost of print colour on acceptance of their article.