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Neuroglobin attenuates Alzheimer‐like tau hyperphosphorylation by activating Akt signaling
Author(s) -
Chen LiMing,
Xiong YanSi,
Kong FanLi,
Qu Min,
Wang Qun,
Chen XiaoQian,
Wang JianZhi,
Zhu LingQiang
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07275.x
Subject(s) - neuroglobin , hyperphosphorylation , protein kinase b , phosphorylation , gsk 3 , gsk3b , neurodegeneration , glycogen synthase , kinase , alzheimer's disease , biology , microbiology and biotechnology , chemistry , neuroscience , biochemistry , medicine , globin , hemoglobin , disease
J. Neurochem. (2012) 120 , 157–164. Abstract 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.