双链RNA依赖的蛋白激酶与阿尔茨海默病相关性研究进展
Research Advances in the Association Between Alzheimer’s Disease and Double-Stranded RNA-Dependent Protein Kinase
查看参考文献74篇
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文摘
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阿尔茨海默病(AD)是一种严重威胁人类健康的疾病,也是引起人类死亡的三大因素之一。双链RNA依赖的蛋白激酶(PKR)又称为前炎症细胞因子,是人类先天免疫干扰素刺激因子之一。在AD发生和发展中, PKR表达上调并持续激活,一方面引发脑组织细胞发生整合应激反应,另一方面间接上调β位淀粉样前体蛋白裂解酶1的表达,促进β淀粉样蛋白(Aβ)的积累,而Aβ的积累又可以激活PKR,进一步促进Aβ的积累,形成一个Aβ持续积累的循环。PKR还可以促进Tau蛋白磷酸化,降低神经细胞微管稳定性。脑组织炎症反应、Aβ的积累所引起神经毒性和微管稳定性的破坏会导致AD发生发展,引起患者记忆和认知的下降,因此PKR是AD发生发展中的关键分子。有效进行PKR检测可以预测AD进展,为临床治疗AD提供先机。目前PKR已成为研发治疗AD药物的靶点,因此靶向PKR的抑制剂有望控制PKR的活性,从而有效控制AD发生发展。 |
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其他语种文摘
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Alzheimer’s disease (AD) is a severe threat to human health and one of the three major causes of human death. Double-stranded RNA-dependent protein kinase (PKR) is an interferon-induced protein kinase involved in innate immunity. In the occurrence and development of AD, PKR is upregulated and continuously activated. On the one hand, the activation of PKR triggers an integrated stress response in brain cells. On the other hand, it indirectly upregulates the expression of β-site amyloid precursor protein cleaving enzyme 1 and facilitates the accumulation of amyloid-β protein (Aβ), which could activate PKR activator to further activate PKR, thus forming a sustained accumulation cycle of Aβ. In addition, PKR can promote Tau phosphorylation, thereby reducing microtubule stability in nerve cells. Inflammation in brain tissue, neurotoxicity resulted from Aβ accumulation, and disruption of microtubule stability led to the progression of AD and the declines of memory and cognitive function. Therefore, PKR is a key molecule in the development and progression of AD. Effective PKR detection can aid in the diagnosis and prediction of AD progression and provide opportunities for clinical treatment. The inhibitors targeting PKR are expected to control the activity of PKR, thereby controlling the progression of AD. Therefore, PKR could be a target for the development of therapeutic drugs for AD. |
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来源
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中国医学科学院学报
,2024,46(3):425-434 【核心库】
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DOI
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10.3881/j.issn.1000-503X.15792
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关键词
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阿尔茨海默病
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双链RNA依赖的蛋白激酶
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β淀粉样蛋白
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Tau蛋白
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地址
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1.
南昌大学抚州医学院, 江西, 抚州, 344000
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南昌大学抚州医学院慢病研究重点实验室, 江西, 抚州, 344000
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井冈山大学医学部, 江西, 吉安, 343009
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语种
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中文 |
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文献类型
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综述型 |
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ISSN
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1000-503X |
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学科
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基础医学 |
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基金
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国家自然科学基金
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江西省自然科学基金
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江西省教育厅重点项目
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文献收藏号
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CSCD:7802604
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