IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline

Fu, A. K. Y. et al. (2016) IL-33 ameliorates Alzheimer’s disease-like pathology and cognitive decline. Proceedings of the National Academy of Sciences of the United States of America, 113(19), E2705-E2713. (doi: 10.1073/pnas.1604032113) (PMID:27091974) (PMCID:PMC4868478)

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Abstract

Alzheimer’s disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of β-amyloid (Aβ) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aβ levels and amyloid plaque deposition by promoting the recruitment and Aβ phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1β, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Liew, Prof Foo
Authors: Fu, A. K. Y., Hung, K.-W., Yuen, M. Y. F., Zhou, X., Mak, D. S. Y., Chan, I. C. W., Cheung, T. H., Zhang, B., Fu, W.-Y., Liew, F. Y., and Ip, N. Y.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
ISSN:0027-8424
ISSN (Online):1091-6490
Copyright Holders:Copyright © 2016 The Authors
First Published:First published in Proceedings of the National Academy of Sciences of the United States of America 113(19):E2705–E2713
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
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