小胶质细胞
神经炎症
星形胶质细胞
兴奋剂
受体
化学
炎症
阿尔茨海默病
细胞生物学
免疫学
神经科学
医学
生物
内科学
生物化学
中枢神经系统
疾病
作者
Yipeng Zhao,Siyu Tian,Jie Zhang,Xi Cheng,Wenping Huang,Guoliang Cao,Yan‐Zhong Chang,Hai Wang,Guangjun Nie,Wei Qiu
出处
期刊:Nano Today
[Elsevier]
日期:2022-06-01
卷期号:44: 101457-101457
被引量:12
标识
DOI:10.1016/j.nantod.2022.101457
摘要
The neuroinflammation induced by amyloid-β (Aβ) has emerged as an important role in onset and progression of Alzheimer’s disease (AD). Hence, regulating the inflammatory mediators produced by glial cells is valuable for AD treatment. Here we developed a glucagon-like peptide 1 receptor (GLP-1R) agonist with blood-brain barrier (BBB) crossing capability to suppress inflammation induced by microglia and astrocyte. Liraglutide (LRGT) was decorated with angiopep-2 peptide and assembled with polyethylene glycol (PEG) to form a nanostructure (pALRGT), showing a higher brain accumulation than free LRGT. Treatment with pALRGT nanostructures could inhibit the secretion of pro-inflammatory cytokines from the activated microglia through PI3K-AKT/NF-κB pathways. Meanwhile, pALRGT nanostructures promoted the differentiation of astrocytes into protective A2 type and secreted IL-3 for Aβ peptide clearance. Consequently, pALRGT nanostructures significantly alleviated the progression of Aβ peptide induced AD in mice. This study demonstrates a novel strategy to modulate microglia activation and astrocyte reactivity for alleviating the progression of AD.
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