title: Neuroglobin attenuates Alzheimer-like tau hyperphosphorylation by activating Akt signaling.
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.
authors.affiliation: Pathophysiology Department, Key Laboratory of Neurological Disease of Education Committee of China, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Chen
authors.forename: Yan-Si
authors.initials: YS
authors.lastname: Xiong
authors.forename: Fan-Li
authors.initials: FL
authors.lastname: Kong
authors.forename: Min
authors.initials: M
authors.lastname: Qu
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Xiao-Qian
authors.initials: XQ
authors.lastname: Chen
authors.forename: Jian-Zhi
authors.initials: JZ
authors.lastname: Wang
authors.forename: Ling-Qiang
authors.initials: LQ
authors.lastname: Zhu
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D005914:Globins / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000096:biosynthesis; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D000078787:Neuroglobin; D010766:Phosphorylation / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D016875:tau Proteins; D005914:Globins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3