Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau. P301S mouse model of Alzheimer's disease and frontotemporal dementia
文献类型:期刊论文
作者 | Ji, Mei1,2; Xie, Xi-xiu1; Liu, Dong-qun1,2; Yu, Xiao-lin1; Zhang, Yue1,3; Zhang, Ling-xiao1,2; Wang, Shao-wei1; Huang, Ya-ru1,2; Liu, Rui-tian1 |
刊名 | ALZHEIMERS RESEARCH & THERAPY
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出版日期 | 2018-06-19 |
卷号 | 10页码:15 |
关键词 | Alzheimer's Disease Frontotemporal Dementia Hepatitis b Core Protein Truncated Tau Neurofibrillary Tangles Virus-like Particles (Vlps) Vaccine |
ISSN号 | 1758-9193 |
DOI | 10.1186/s13195-018-0378-7 |
英文摘要 | Background: Truncated mis-disordered tau protein plays an important role in the pathogenesis of Alzheimer's disease (AD) and frontotemporal dementia (FTD). Tau(294-305), an epitope in the truncated tau, is essential for pathological tau-tau interaction and aggregation. A tau(294-305)-targeted approach may have beneficial effects in the treatment of AD and FTD. Methods: In this study, we genetically fused tau(294-305) epitope to the hepatitis B virus core protein (HBc) major immunodominant region (MIR) (with the resultant protein termed T294-HBc), and we subcutaneously immunized a Tau.P301S transgenic mouse model of FTD and AD with T294-HBc four times. The levels and characteristics of antibodies induced by T294-HBc were determined by enzyme-linked immunosorbent assay. The effect of T294-HBc on the cognitive deficits of Tau. P301S mice was tested using the Morris water maze test, novel object recognition, and a Y-maze test. Western blot analysis and IHC were applied to measure the effect of T294-HBc on tau pathologies and neuroinflammation in the mouse brains. Results: The results showed that T294-HBc self-assembled into HBc chimeric virus-like particles (VLPs) with tau294-305 displayed on the surface and that it induced high antibody titers specifically against the mis-disordered truncated tau. Further investigation showed that these antibodies simultaneously bound to microtubule-binding regions 1-4 (MTBR1-4) [tau(263-274), tau(294-305,) tau(325-336,) tau(357-368) and tau(294-305)(P301S)]. Moreover, T294-HBc VLP vaccination significantly ameliorated memory and cognitive decline; reduced the levels of AT8-positive tau, truncated tau monomer, and oligomer; attenuated microgliosis and astrogliosis; and rescued synaptic deficits in Tau.P301S transgenic mice. Conclusions: T294-HBc VLP vaccine elicited strong immune response and alleviated cognitive deficits and neuropathology progression in Tau. P301S mice, indicating that the T294-HBc VLP vaccine has promising therapeutic potential for the treatment of AD and FTD. |
WOS关键词 | Virus-like Particles ; In-vivo ; Neurofibrillary Degeneration ; Corticobasal Degeneration ; Structural Determinants ; Truncated Tau ; Immunotherapy ; Protein ; Pathology ; Tauopathy |
资助项目 | Strategic Leading Project of China Academy of Sciences[XDA 2040215] ; National Science and Technology Major Projects of New Drugs[2015ZX09102015] |
WOS研究方向 | Neurosciences & Neurology |
语种 | 英语 |
WOS记录号 | WOS:000435568600001 |
出版者 | BIOMED CENTRAL LTD |
资助机构 | Strategic Leading Project of China Academy of Sciences ; National Science and Technology Major Projects of New Drugs |
源URL | [http://ir.ipe.ac.cn/handle/122111/24862] ![]() |
专题 | 中国科学院过程工程研究所 |
通讯作者 | Liu, Rui-tian |
作者单位 | 1.Chinese Acad Sci, Natl Key Lab Biochem Engn, Inst Proc Engn, Beijing 100190, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Shandong Agr Univ, Shandong Prov Key Lab Anim Biotechnol & Dis Contr, Tai An 271018, Shandong, Peoples R China |
推荐引用方式 GB/T 7714 | Ji, Mei,Xie, Xi-xiu,Liu, Dong-qun,et al. Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau. P301S mouse model of Alzheimer's disease and frontotemporal dementia[J]. ALZHEIMERS RESEARCH & THERAPY,2018,10:15. |
APA | Ji, Mei.,Xie, Xi-xiu.,Liu, Dong-qun.,Yu, Xiao-lin.,Zhang, Yue.,...&Liu, Rui-tian.(2018).Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau. P301S mouse model of Alzheimer's disease and frontotemporal dementia.ALZHEIMERS RESEARCH & THERAPY,10,15. |
MLA | Ji, Mei,et al."Hepatitis B core VLP-based mis-disordered tau vaccine elicits strong immune response and alleviates cognitive deficits and neuropathology progression in Tau. P301S mouse model of Alzheimer's disease and frontotemporal dementia".ALZHEIMERS RESEARCH & THERAPY 10(2018):15. |
入库方式: OAI收割
来源:过程工程研究所
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