Pathophysiology Department, Key Laboratory of Neurological Disease of Education Committee of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Neurochem. 2012 Jan;120(1):157-64. doi: 10.1111/j.1471-4159.2011.07275.x. Epub 2011 May 13.
Neuroglobin (Ngb) is a recently identified member of hemoglobin family, distributed mainly in central and peripheral nervous systems. Recent studies suggest that Ngb can protect neural cells from β-amyloid-induced toxicity in Alzheimer disease (AD). Hyperphosphorylation of tau is another characterized pathological hallmark in the AD brains; however, it is not reported whether Ngb also affects tau phosphorylation. In this study, we found that the level of Ngb was significantly reduced in Tg2576 mice (a recognized mouse model of AD) and TgMAPt mice, and the level of Ngb was negatively correlated with tau phosphorylation. Over-expression of Ngb attenuates tau hyperphosphorylation at multiple AD-related sites induced by up-regulation of glycogen synthase kinase-3β (GSK-3β), a crucial tau kinase. While Ngb activates Akt and thus inhibits GSK-3β, simultaneously inhibition of Akt abolishes the effects of Ngb on GSK-3β inhibition and tau hyperphosphorylation. Our data indicate that Ngb may attenuate tau hyperphosphorylation through activating Akt signaling pathway, implying a therapeutic target for AD.
神经球蛋白（Ngb）是血红蛋白家族中最近被发现的成员，主要分布于中枢和外周神经系统。最近的研究表明，Ngb 可以保护神经细胞免受阿尔茨海默病（AD）中β-淀粉样蛋白诱导的毒性。tau 蛋白过度磷酸化是 AD 脑中另一个特征性的病理标志；然而，目前尚不清楚 Ngb 是否也会影响 tau 磷酸化。在这项研究中，我们发现 Tg2576 小鼠（公认的 AD 小鼠模型）和 TgMAPt 小鼠的 Ngb 水平显著降低，且 Ngb 水平与 tau 磷酸化呈负相关。Ngb 的过表达可减轻由糖原合成酶激酶-3β（GSK-3β）上调诱导的多个与 AD 相关的 tau 过度磷酸化位点的磷酸化，GSK-3β 是一种关键的 tau 激酶。Ngb 激活 Akt，从而抑制 GSK-3β，而 Akt 的抑制则消除了 Ngb 对 GSK-3β 抑制和 tau 过度磷酸化的影响。我们的数据表明，Ngb 可能通过激活 Akt 信号通路来减轻 tau 过度磷酸化，这为 AD 提供了一个治疗靶点。
Zotero 插件