Stroke & Dementia Research Centre, Division of Clinical Sciences, St Georges University of London, London, UK.
Neuropathol Appl Neurobiol. 2013 Oct;39(6):623-33. doi: 10.1111/nan.12023.
Serum- and glucocorticoid-inducible kinase 1 (SGK1) protects neuronal cells from injury stimuli in vitro, and exerts anti-apoptotic effects via downstream targets including the forkhead-like transcription factor FOXO3a. SGK1 is a homolog of Akt, a related survival kinase that is up-regulated in Alzheimer's disease (AD). Here we aimed to examine the expression pattern of SGK1 and FOXO3a in aged human cerebral cortex.
Cortical tissue from aged donors without brain disease (aged controls, AC, n = 19) and from severe AD patients (Braak stage V-VI; n = 14) were examined by immunohistochemistry and immunoblot analysis.
SGK1 was present in all samples (detected by immunohistochemistry and immunoblotting). Large cortical neuronal cells were strongly positive for SGK1, with predominantly nuclear labelling. Some astrocytes and oligodendrocytes were also labelled. SGK1 was not seen in nerve tracts (axons or myelin) and rarely seen in CD68-positive cells (microglia, perivascular macrophages) or vascular cells (myocytes or endothelia). The fraction of large cortical neurones with nuclear FOXO3a was lower in AD cases relative to AC (54%, 70%, respectively, P < 0.001). In immunoblots no difference in SGK1 abundance was detected between AC and AD tissues. Phosphorylation of NDRG1 (an SGK1-specific target) was greater in AD, relative to AC cases (approximately twofold, P = 0.023).
Neuronal expression of SGK1 in aged human brain and its nuclear compartmentalization suggest a possible neuroprotective role. FOXO3a and NDRG1 data suggest augmented SGK1 activity (as reported for Akt) in severe AD. Increased intracellular SGK1 may complement enhanced Akt, with a distinct subcellular localization.
血清和糖皮质激素诱导激酶 1（SGK1）可在体外保护神经元细胞免受损伤刺激，并通过下游靶点（包括叉头样转录因子 FOXO3a）发挥抗凋亡作用。SGK1 是 Akt 的同源物，Akt 是一种相关的存活激酶，在阿尔茨海默病（AD）中上调。在这里，我们旨在研究 SGK1 和 FOXO3a 在老年人大脑皮质中的表达模式。
通过免疫组织化学和免疫印迹分析，检查无脑部疾病的老年供体（老年对照组，AC，n=19）和严重 AD 患者（Braak 阶段 V-VI；n=14）的皮质组织。
SGK1 在所有样本中均存在（通过免疫组织化学和免疫印迹检测）。大皮质神经元细胞对 SGK1 呈强阳性，主要为核标记。一些星形胶质细胞和少突胶质细胞也被标记。SGK1 未见于神经束（轴突或髓鞘），也很少见于 CD68 阳性细胞（小胶质细胞、血管周围巨噬细胞）或血管细胞（肌细胞或内皮细胞）。与 AC 相比，AD 病例中具有核 FOXO3a 的大皮质神经元比例较低（分别为 54%、70%，P<0.001）。在免疫印迹中，AC 和 AD 组织之间未检测到 SGK1 丰度的差异。与 AC 病例相比，AD 病例中 NDRG1（SGK1 的特定靶标）的磷酸化程度更高（约两倍，P=0.023）。
SGK1 在老年人大脑皮质中的神经元表达及其核区室化表明其可能具有神经保护作用。FOXO3a 和 NDRG1 数据表明，在严重 AD 中 SGK1 活性增强（如 Akt 报道）。细胞内 SGK1 的增加可能与增强的 Akt 相辅相成，具有不同的亚细胞定位。
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