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

摘要: The 5'-AMP-activated protein kinase (AMPK), which is a sensor of cellular energy, regulates neuronal survival and energy homeostasis. However, the roles AMPK in pathogenesis Alzheimer's disease (AD) are unclear. senescence-accelerated mouse prone 8 (SAMP8) strain characterized by deficits learning memory, exhibits pathological characteristics AD as early 5 months age, being increasingly recognized model AD. Here, we investigated relationship between activation phosphorylation tau brain young (2-month-old) SAMP8 animals differentiated SH-SY5Y cells. Upregulation p-AMPK, p-ACC, p-GSK3βS9 downregulation p-tau396 sirtuin 1 (Sirt1) were observed cerebral cortex mice compared with that age-matched SAMR1 animals. hippocampal levels p-AMPK not significantly different from those SAMR1, whereas upregulation sirt1 was hippocampus mice. Consistent vivo findings cortex, cells upregulated but downregulated p-tau396, it had no significant effect on p-tau262 expression. In addition, AMPK-mediated inhibition expression attenuated okadaic acid, phosphatase 2A (PP2A) inhibitor. Taken together, our data showed inhibits GSK3β- PP2A-dependent manner, suggest differential regulation plays compensatory role against accelerated senescence this animal model.