Activation of the 5'-AMP-Activated Protein Kinase in the Cerebral Cortex of Young Senescence-Accelerated P8 Mice and Association with GSK3β- and PP2A-Dependent Inhibition of p-tau396 Expression

Journal of Alzheimer's Disease : JAD
Hak-Su KimJu-Hee Kang

Abstract

The 5'-AMP-activated protein kinase (AMPK), which is a sensor of cellular energy, regulates neuronal survival and energy homeostasis. However, the roles of AMPK in the pathogenesis of Alzheimer's disease (AD) are unclear. The senescence-accelerated mouse prone 8 (SAMP8) strain is characterized by deficits in learning and memory, exhibits pathological characteristics of AD as early as 5 months of age, and is being increasingly recognized as a model of AD. Here, we investigated the relationship between AMPK activation and phosphorylation of the tau protein in the brain of young (2-month-old) SAMP8 animals and in differentiated SH-SY5Y cells. Upregulation of p-AMPK, p-ACC, and p-GSK3βS9 and downregulation of p-tau396 and sirtuin 1 (Sirt1) were observed in the cerebral cortex of young SAMP8 mice compared with that of age-matched SAMR1 animals. The hippocampal levels of p-AMPK and p-tau396 in SAMP8 animals were not significantly different from those of SAMR1, whereas upregulation of p-GSK3βS9 and downregulation of sirt1 was observed in the hippocampus of SAMP8 mice. Consistent with in vivo findings in the cortex, AMPK activation in SH-SY5Y cells upregulated p-GSK3βS9 but downregulated p-tau396, whereas it had no significant effect o...Continue Reading

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Citations

Jun 14, 2015·Journal of Neural Transmission·Ting-Ting YangChu-Wan Lee
Jul 6, 2016·International Neurourology Journal·Geun Ho ParkChang-Shin Park
Aug 23, 2020·International Journal of Molecular Sciences·Sakulrat MankhongJu-Hee Kang
Mar 10, 2020·BioMed Research International·Brhane Teklebrhan AssefaMeles Tekie Gidey
Nov 25, 2016·Neurochemical Research·Henryk JęśkoJoanna B Strosznajder
Jul 12, 2020·Journal of Alzheimer's Disease : JAD·Kyung-Lim JoaJu-Hee Kang
Oct 8, 2020·International Journal of Molecular Sciences·Alejandro Sánchez-MelgarMairena Martín
Dec 12, 2020·Behavioural Brain Research·Meixiang ChenFeng Jin
Oct 12, 2021·Expert Opinion on Drug Metabolism & Toxicology·Natalie R NeumannVasilis Vasiliou

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