Yi Gong, Xing-Yang Xiao, You-Sheng Hu, Yi-Wei Xie, Zhi-Hui Wu
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引用次数: 0
摘要
双链RNA依赖性蛋白激酶(PKR)是一种干扰素诱导的蛋白激酶,参与先天性免疫。在阿尔茨海默病(AD)的发生和发展过程中,PKR被上调并持续激活。在 AD 的发生和发展过程中,PKR 会被上调并持续激活,一方面,PKR 的激活会引发脑细胞的综合应激反应;另一方面,PKR 会间接上调 β 位淀粉样前体蛋白裂解酶 1 的表达,促进淀粉样-β 蛋白(Aβ)的积累,从而激活 PKR 激活因子,进一步激活 PKR,形成 Aβ 的持续积累循环。此外,PKR 还能促进 Tau 磷酸化,从而降低神经细胞中微管的稳定性。脑组织炎症、Aβ 累积导致的神经毒性以及微管稳定性的破坏导致了 AD 的发展以及记忆和认知功能的下降。有效检测PKR有助于诊断和预测AD的进展,并为临床治疗提供机会。
[Research Advances in the Association Between Alzheimer's Disease and Double-Stranded RNA-Dependent Protein Kinase].
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.
期刊介绍:
Acta Academiae Medicinae Sinicae was founded in February 1979. It is a comprehensive medical academic journal published in China and abroad, supervised by the Ministry of Health of the People's Republic of China and sponsored by the Chinese Academy of Medical Sciences and Peking Union Medical College.
The journal mainly reports the latest research results, work progress and dynamics in the fields of basic medicine, clinical medicine, pharmacy, preventive medicine, biomedicine, medical teaching and research, aiming to promote the exchange of medical information and improve the academic level of medicine. At present, the journal has been included in 10 famous foreign retrieval systems and their databases [Medline (PubMed online version), Elsevier, EMBASE, CA, WPRIM, ExtraMED, IC, JST, UPD and EBSCO-ASP]; and has been included in important domestic retrieval systems and databases [China Science Citation Database (Documentation and Information Center of the Chinese Academy of Sciences), China Core Journals Overview (Peking University Library), China Science and Technology Paper Statistical Source Database (China Science and Technology Core Journals) (China Institute of Scientific and Technological Information), China Science and Technology Journal Paper and Citation Database (China Institute of Scientific and Technological Information)].