title: Overexpression of heme oxygenase 1 causes cognitive decline and affects pathways for tauopathy in mice.
abstract: The stress protein heme oxygenase-1 (HO-1) is upregulated and co-localizes to pathological features, including tauopathies in the brains of individuals with Alzheimer's disease. However, the relationship between HO-1 and Alzheimer's disease remains unclear. In our previous research, the long-term overexpression of HO-1 was shown to promote tau aggregation by inducing tau phosphorylation in the mouse brain. In this study, we found that the long-term overexpression of HO-1 led to cognitive decline in transgenic mice, as determined by the water maze test, and that HO-1 can affect two pathways for tauopathy. Through one pathway, HO-1 promotes the expression of CDK5 by accumulating reactive oxygen species, which are produced by HO-1 downstream products of iron in neuro2a cell lines and mouse brain. Through the second pathway, HO-1 induces tau truncation at D421 in vivo and in vitro. Clearly, there is a HO-1-dependent mechanism responsible for tau protein phosphorylation and tau truncation in vivo and in vitro. Taken together, our results suggest that HO-1 plays an important role in the disease process of tauopathies in AD.
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hui
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Rongzhang
authors.initials: R
authors.lastname: He
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Yanze
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Lisha
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, China Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Harbin, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Gao
authors.affiliation: Department of Gerontology, The First Hospital of Harbin Medical University, Harbin, China.
authors.forename: Shanshun
authors.initials: S
authors.lastname: Luo
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D003072:Cognition Disorders / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics*; D018698:Glutamic Acid / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism / Q000494:pharmacology; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation / Q000187:drug effects; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D065853:Spatial Learning / Q000502:physiology; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology
chemical_list: D011524:Protoporphyrins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; C007095:cobaltiprotoporphyrin; D007501:Iron; D051547:Heme Oxygenase-1; D051360:Cyclin-Dependent Kinase 5
keywords: Alzheimer's disease; CDK5; heme oxygenase-1; iron; tau truncation; tauopathies