期刊
NANO TODAY
卷 44, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2022.101457
关键词
Alzheimer's disease; GLP-1R agonist; Blood-brain barrier; Microglia; Astrocyte
资金
- National Natural Science Foundation of China [32070962, 81771300, 81971140, 82001284]
- Chinese Postdoctoral Science Foundation [2020M672994]
- Natural Science Foundation of Guangdong Province [2020A1515010053]
Using modified liraglutide nanostructures can inhibit neuroinflammation and promote the differentiation of astrocytes into protective cell types, thereby significantly alleviating the progression of Alzheimer's disease.
The neuroinflammation induced by amyloid-beta (A beta) 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-kappa B pathways. Meanwhile, pALRGT nanostructures promoted the differentiation of astrocytes into protective A2 type and secreted IL-3 for A beta peptide clearance. Consequently, pALRGT nanostructures significantly alleviated the progression of A beta peptide induced AD in mice. This study demonstrates a novel strategy to modulate microglia activation and astrocyte reactivity for alleviating the progression of AD. (c) 2022 Published by Elsevier Ltd.
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