Research Advances in the Association Between Alzheimer's Disease and Double-Stranded RNA-Dependent Protein Kinase
10.3881/j.issn.1000-503X.15792
- VernacularTitle:双链RNA依赖的蛋白激酶与阿尔茨海默病相关性研究进展
- Author:
Yi GONG
1
;
Xingyang XIAO
;
Yousheng HU
;
Yiwei XIE
;
Zhihui WU
Author Information
1. 南昌大学抚州医学院,江西抚州 344000
- Keywords:
Alzheimer's disease;
double-stranded RNA-dependent protein kinase;
amyloid-beta;
Tau
- From:
Acta Academiae Medicinae Sinicae
2024;46(3):425-434
- CountryChina
- Language:Chinese
-
Abstract:
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 continu-ously 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 3-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 Aβaccumulation,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 treat-ment.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.
