• Lu Wang, Yingjuan Wei, Zhenzhou Sun, Lin-Hua Jiang, Yaling Yin, Panpan Zheng, Yun Fu, Hongwei Wang, Changzheng Li, and Jian-Zhi Wang.
• Henan Key Laboratory of Neurorestoratology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China; Department of Physiology and Pathophysiology, Xinxiang Medical University, Xinxiang, China. Electronic address: wllisa2004@126.com.
• Neuroscience. 2023 Aug 21; 526: 196203196-203.

AbstractTau protein hyperphosphorylation and formation of intracellular neurofibrillary tangles (NFTs) are one of the histopathological hallmarks of Alzheimer's disease (AD) and positively correlated with the severity of AD symptoms. NFTs contain a large number of metal ions that play an important role in regulating tau protein phosphorylation and AD progression. Extracellular tau induces primary phagocytosis of stressed neurons and neuronal loss by activating microglia. Here, we studied the effects of a multi-metal ion chelator, DpdtpA, on tau-induced microglial activation and inflammatory responses and the underlying mechanisms. Treatment with DpdtpA attenuated the increase in the expression of NF-κB and production of inflammatory cytokines, IL-1β, IL-6 and IL-10, in rat microglial cells induced by expression of human tau40 proteins. Treatment with DpdtpA also suppressed tau protein expression and phosphorylation. Moreover, treatment with DpdtpA prevented tau-induced activation of glycogen synthase kinase-3β (GSK-3β) and inhibition of phosphatidylinositol-3-hydroxy kinase (PI3K)/AKT. Collectively, these results show that DpdtpA can attenuate tau phosphorylation and inflammatory responses of microglia by regulating the PI3K/AKT/GSK-3β signal pathways, providing a new option to alleviate neuroinflammation for the treatment of AD.Copyright © 2023 IBRO. Published by Elsevier Ltd. All rights reserved.

26 keywords...

hide…