小胶质细胞
神经保护
串扰
神经科学
活性氧
肿瘤微环境
β淀粉样蛋白
胶束
化学
细胞生物学
医学
疾病
生物
炎症
免疫学
免疫系统
病理
物理
物理化学
光学
水溶液
作者
Yifei Lü,Zhongyuan Guo,Yujie Zhang,Chao Li,Yu Zhang,Qin Guo,Qinjun Chen,Han Y. H. Chen,Xi He,Lisha Li,Chunhui Ruan,Tao Sun,Bin Ji,Wenyue Lu,Chen Jiang
标识
DOI:10.1002/advs.201801586
摘要
Current strategies for Alzheimer's disease (AD) treatments focus on pathologies in the late stage of the disease progression. Poor clinical outcomes are displayed due to the irreversible damages caused by early microglia abnormality which triggers disease development before identical symptoms emerge. Based on the crosstalk between microglia and brain microenvironment, a reactive oxygen species (ROS)-responsive polymeric micelle system (Ab-PEG-LysB/curcumin (APLB/CUR)) is reported to normalize the oxidative and inflammatory microenvironment and reeducate microglia from an early phase of AD. Through an β-amyloid (Aβ) transportation-mimicked pathway, the micelles can accumulate into the diseased regions and exert synergistic effects of polymer-based ROS scavenging and cargo-based Aβ inhibition upon microenvironment stimuli. This multitarget strategy exhibits gradual correction of the brain microenvironment, efficient neuroprotection, and microglia modulation, leading to decreased Aβ plaque burdens and consequently enhanced cognitive functions in APPswe/PSEN1dE9 model mice. The results indicate that microglia can be exploited as an early target for AD treatment and their states can be controlled via microenvironment modulation.
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