title: Triptolide treatment reduces Alzheimer's disease (AD)-like pathology through inhibition of BACE1 in a transgenic mouse model of AD.
abstract: The complex pathogenesis of Alzheimer's disease (AD) involves multiple contributing factors, including amyloid β (Aβ) peptide accumulation, inflammation and oxidative stress. Effective therapeutic strategies for AD are still urgently needed. Triptolide is the major active compound extracted from Tripterygium wilfordii Hook.f., a traditional Chinese medicinal herb that is commonly used to treat inflammatory diseases. The 5-month-old 5XFAD mice, which carry five familial AD mutations in the β-amyloid precursor protein (APP) and presenilin-1 (PS1) genes, were treated with triptolide for 8 weeks. We observed enhanced spatial learning performances, and attenuated Aβ production and deposition in the brain. Triptolide also inhibited the processing of amyloidogenic APP, as well as the expression of βAPP-cleaving enzyme-1 (BACE1) both in vivo and in vitro. In addition, triptolide exerted anti-inflammatory and anti-oxidative effects on the transgenic mouse brain. Triptolide therefore confers protection against the effects of AD in our mouse model and is emerging as a promising therapeutic candidate drug for AD.
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Department of Medicine, Dezhou University, Dezhou 253023, PR China.
authors.forename: Shuqin
authors.initials: S
authors.lastname: Cui
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China.
authors.forename: Hailong
authors.initials: H
authors.lastname: Song
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Haiting
authors.initials: H
authors.lastname: An
authors.affiliation: Capital Medical University Yanjing Medical College, Beijing 101300, PR China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Jianliang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Feilong
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Guanzheng
authors.initials: G
authors.lastname: Hu
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Physiology and Biophysics, State University of New York at Buffalo, Buffalo, NY 14214, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China. zhengyan@ccmu.edu.cn xmwang@ccmu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Physiology, Department of Neurobiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Capital Medical University, Beijing 100069, PR China. Beijing Institute for Brain Disorders, Beijing 100069, PR China. zhengyan@ccmu.edu.cn xmwang@ccmu.edu.cn.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D000975:Antioxidants / Q000737:chemistry; D016282:Aspartic Acid Endopeptidases / Q000235:genetics*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology*; D004852:Epoxy Compounds / Q000494:pharmacology; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007858:Learning / Q000187:drug effects; D018782:Maze Learning; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D010616:Phenanthrenes / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology
chemical_list: D016564:Amyloid beta-Protein Precursor; D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004224:Diterpenes; D004852:Epoxy Compounds; D007166:Immunosuppressive Agents; D010616:Phenanthrenes; D010936:Plant Extracts; C001899:triptolide; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; C509282:Bace1 protein, mouse
keywords: 5XFAD mice; Alzheimer’s disease; Amyloid β; BACE1; Inflammation; Triptolide