Roles of AMP-activated Protein Kinase in Alzheimer’s Disease

摘要: AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis and central player in glucose lipid metabolism, is potentially implicated the pathogenesis Alzheimer’s disease (AD). AMPK activity decreases AD brain, indicating decreased mitochondrial biogenesis function. Emerging evidence demonstrates that activation potential target for improving perturbed brain metabolism involved AD. The roles include β-amyloid (Aβ) generation tau phosphorylation. In particular, may regulate Aβ through modulating neuronal cholesterol sphingomyelin levels regulating APP distribution rafts. activated by phosphorylation Thr-172 LKB1 complex response to increase AMP/ATP ratio calmodulin-dependent kinase-beta elevated Ca2+ levels, which contributes generation. physiological can at Ser-262. also directly phosphorylate Thr-231 Ser-396/404. Furthermore, mTOR signaling facilitate autophagy promotes lysosomal degradation Aβ. However, has non-neuroprotective property lead detrimental outcomes, including Therefore, it still unclear whether could serve therapeutic AD, hence, further studies will be needed clarify role