An "Amyloid-beta Cleaner" for the Treatment of Alzheimer's Disease by Normalizing Microglial Dysfunction | |
Liu, Ruiyuan1,2; Yang, Jun2; Liu, Linying1,2; Lu, Zhiguo1,2; Shi, Zhuyan1,2; Ji, Weihong1,2; Shen, Jie1,2; Zhang, Xin2 | |
刊名 | ADVANCED SCIENCE |
2019-11-22 | |
页码 | 12 |
关键词 | Alzheimer's Disease a Beta Microglia Neuroinflammation Phagocytosis |
DOI | 10.1002/advs.201901555 |
英文摘要 | Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by progressive cognitive and memory loss. The vicious circle between dysfunctional microglia and amyloid-beta (A beta) is a crucial pathological event and accelerates the progression of AD. Herein, a zwitterionic poly(carboxybetaine) (PCB)-based nanoparticle (MCPZFS NP) with normalizing the dysfunctional microglia and A beta recruitment is established for the treatment of AD. Compared with the neural polyethylene glycol (PEG)-based nanoparticles (MEPZFS NPs), the MCPZFS NPs significantly alleviate the priming of microglia by decreasing the level of proinflammatory mediators and promoting the secretion of BDNF. Most importantly, quite different from PEG, the PCB-based NPs exhibit the behavior to recruit A beta into microglia, which significantly enhances the A beta phagocytosis. Moreover, the A beta degradation is changed from the conventional lysosomal/autophagy to the proteasomal pathway in the presence of MCPZFS NPs. After the treatment with MCPZFS NPs, the A beta burden, neuron damages, memory deficits, and neuroinflammation of APPswe/PS1dE9 mice are significantly attenuated in the brain. Therefore, the PCB-based MCPZFS NPs have great potential to serve as an "A beta cleaner" and provide a new insight into the therapeutic strategy for AD therapy. |
资助项目 | National High Technology Research and Development Program[2016YFA0200303] ; National Natural Science Foundation of China[31771095] ; National Natural Science Foundation of China[21875254] ; National Natural Science Foundation of China[51573188] ; Beijing Natural Science Foundation[L172046] ; Beijing Natural Science Foundation[2192057] |
WOS关键词 | Accelerated Blood Clearance ; Small Interfering Rna ; Cellular Uptake ; Liposomes ; Delivery ; Aggregation ; Trafficking ; Efficiency ; Impairment ; Peptide |
WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
语种 | 英语 |
出版者 | WILEY |
WOS记录号 | WOS:000497900400001 |
资助机构 | National High Technology Research and Development Program ; National Natural Science Foundation of China ; Beijing Natural Science Foundation |
内容类型 | 期刊论文 |
源URL | [http://ir.ipe.ac.cn/handle/122111/38309] |
专题 | 中国科学院过程工程研究所 |
通讯作者 | Zhang, Xin |
作者单位 | 1.Univ Chinese Acad Sci, Sch Chem Engn, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Inst Proc Engn, State Key Lab Biochem Engn, Beijing 100190, Peoples R China |
推荐引用方式 GB/T 7714 | Liu, Ruiyuan,Yang, Jun,Liu, Linying,et al. An "Amyloid-beta Cleaner" for the Treatment of Alzheimer's Disease by Normalizing Microglial Dysfunction[J]. ADVANCED SCIENCE,2019:12. |
APA | Liu, Ruiyuan.,Yang, Jun.,Liu, Linying.,Lu, Zhiguo.,Shi, Zhuyan.,...&Zhang, Xin.(2019).An "Amyloid-beta Cleaner" for the Treatment of Alzheimer's Disease by Normalizing Microglial Dysfunction.ADVANCED SCIENCE,12. |
MLA | Liu, Ruiyuan,et al."An "Amyloid-beta Cleaner" for the Treatment of Alzheimer's Disease by Normalizing Microglial Dysfunction".ADVANCED SCIENCE (2019):12. |
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