Dauricine Attenuates Spatial Memory Impairment and Alzheimer-Like Pathologies by Enhancing Mitochondrial Function in a Mouse Model of Alzheimer's Disease

被引：24

作者：

Chen, Chongyang ^{[1
]}

Liu, Pan ^{[1
]}

Wang, Jing ^{[1
]}

Yu, Haitao ^{[1
]}

Zhang, Zaijun ^{[2
]}

Liu, Jianjun ^{[1
]}

Chen, Xiao ^{[1
]}

Zhu, Feiqi ^{[3
]}

Yang, Xifei ^{[1
]}

机构：

[1] Shenzhen Ctr Dis Control & Prevent, Shenzhen Key Lab Modern Toxicol, Shenzhen Med Key Discipline Hlth Toxicol 2020 202, Shenzhen, Peoples R China

[2] Jinan Univ, Inst New Drug Res & Guangzhou, Key Lab Innovat Chem Drug Res Cardiocerebrovasc D, Coll Pharm, Guangzhou, Peoples R China

[3] Shenzhen Univ, Cognit Impairment Ward, Neurol Dept, Med Coll,Affiliated Hosp 3, Shenzhen, Peoples R China

来源：

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 8卷

基金：

中国国家自然科学基金;

关键词：

Alzheimer' s disease; dauricine; proteomics; mitochondrial function; synaptic function;

D O I：

10.3389/fcell.2020.624339

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Alzheimer's disease (AD) is characterized by extracellular amyloid plaques composed of beta-amyloid (A beta) and intracellular neurofibrillary tangles containing hyperphosphorylated tau protein. No effective therapy is available for this disease. In this study, we investigated the potential therapeutic effects of dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid, on AD, and found that DAU administration significantly improved cognitive impairments in 3xTg-AD mice by decreasing A beta plaques and hyperphosphorylated tau and increasing the hippocampal ATP level. Proteomic and western blot analyses revealed that DAU treatment mainly modified the expression of proteins involved in mitochondrial energy metabolism, such as Aco2, Ndufs1, Cox5a, and SDHB, and that of synapse-related proteins such as Syn1 and Syn2. Pathway analysis revealed that DAU modulated the tricarboxylic acid cycle, synaptic vesicle cycle, glycolysis, and gluconeogenesis in 3xTg-AD mice. Our study suggests that DAU may be a potential drug for the treatment of AD.

引用

页数：11

共 36 条

[31]

Dauricine inhibits insulin-like growth factor-I-induced hypoxia inducible factor 1α protein accumulation and vascular endothelial growth factor expression in human breast cancer cells [J].