期刊
NEURON
卷 85, 期 3, 页码 519-533出版社
CELL PRESS
DOI: 10.1016/j.neuron.2014.11.020
关键词
-
资金
- NIH [RO1AG32991, R01AG018454]
- NIA [AG046139-01]
Anti-inflammatory strategies are proposed to have beneficial effects in Alzheimer's disease. To explore how anti-inflammatory cytokine signaling affects Ab pathology, we investigated the effects of adeno-associated virus (AAV2/1)-mediated expression of Interleukin (IL)-10 in the brains of APP transgenic mouse models. IL-10 expression resulted in increased Ab accumulation and impaired memory in APP mice. A focused transcriptome analysis revealed changes consistent with enhanced IL-10 signaling and increased ApoE expression in IL-10-expressing APP mice. ApoE protein was selectively increased in the plaque-associated insoluble cellular fraction, likely because of direct interaction with aggregated Ab in the IL-10-expressing APP mice. Ex vivo studies also show that IL-10 and ApoE can individually impair glial Ab phagocytosis. Our observations that IL-10 has an unexpected negative effect on Ab proteostasis and cognition in APP mouse models demonstrate the complex interplay between innate immunity and proteostasis in neurodegenerative diseases, an interaction we call immunoproteostasis.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据