The cell survival kinase SGK1 and its targets FOXO3a and NDRG1 in aged human brain

摘要: Aims Serum- and glucocorticoid-inducible kinase 1 (SGK1) protects neuronal cells from injury stimuli in vitro, exerts anti-apoptotic effects via downstream targets including the forkhead-like transcription factor FOXO3a. SGK1 is a homolog of Akt, related survival that up-regulated Alzheimer's disease (AD). Here we aimed to examine expression pattern FOXO3a aged human cerebral cortex. Methods Cortical tissue donors without brain (aged controls, AC, n = 19) severe AD patients (Braak stage V-VI; n = 14) were examined by immunohistochemistry immunoblot analysis. Results SGK1 was present all samples (detected immunoblotting). Large cortical strongly positive for SGK1, with predominantly nuclear labelling. Some astrocytes oligodendrocytes also labelled. not seen nerve tracts (axons or myelin) rarely CD68-positive (microglia, perivascular macrophages) vascular (myocytes endothelia). The fraction large neurones lower cases relative AC (54%, 70%, respectively, P < 0.001). In immunoblots no difference abundance detected between tissues. Phosphorylation NDRG1 (an SGK1-specific target) greater AD, (approximately twofold, P = 0.023). Conclusions Neuronal its compartmentalization suggest possible neuroprotective role. data augmented activity (as reported Akt) AD. Increased intracellular may complement enhanced distinct subcellular localization.