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Glycogen Synthase Kinase-3β, NLRP3 Inflammasome, and Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD) is the most prevalent cause of dementia worldwide. Because of the progressive neurodegeneration, individual cognitive and behavioral functions are impaired, affecting the quality of life of millions of people. Although the exact pathogenesis of AD has not been fully elucidated, amyloid plaques, neurofibrillary tangles (NFTs), and sustaining neuroinflammation dominate its characteristics. As one of the major tau kinases leading to hyperphosphorylation and aggregation of tau, glycogen synthase kinase-3β (GSK-3β) has been drawing great attention in various AD studies. Another research focus of AD in recent years is the inflammasome, a multiprotein complex acting as a regulator in immunological reactions to exogenous and endogenous danger signals, of which the Nod-like receptor (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome has been studied mostly in AD and proven to play a significant role in AD development by its activation and downstream effects such as caspase-1 maturation and interleukin (IL)-1β release. Studies have shown that the NLRP3 inflammasome is activated in a GSK-3β-dependent way and that inhibition of the NLRP3 inflammasome downregulates GSK-3β, suggesting that these two important proteins are closely related. This article reviews the respective roles of GSK-3β and the NLRP3 inflammasome in AD as well as their relationship and interaction.

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  1. The authors contributed equally to this study.

Authors and Affiliations

  1. Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yue-ran Jia, Zi-qing Guo, Qian Guo & Xiao-chuan Wang

  2. Co-innovation Center of Neuroregeneration, Nantong University, Nantong, 226001, China

    Xiao-chuan Wang

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  1. Yue-ran Jia
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  2. Zi-qing Guo
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Correspondence to Xiao-chuan Wang.

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This work was supported by grants from the National Natural Science Foundation of China (No. 92049107 and No. 31929002), the Innovative Research Groups of the National Natural Science Foundation of China (No. 81721005), and the Academic Frontier Youth Team Project to Xiaochuan Wang from Huazhong University of Science and Technology.

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Jia, Yr., Guo, Zq., Guo, Q. et al. Glycogen Synthase Kinase-3β, NLRP3 Inflammasome, and Alzheimer’s Disease. CURR MED SCI 43, 847–854 (2023). https://doi.org/10.1007/s11596-023-2788-4

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