IPAF inflammasome is involved in interleukin-1β production from astrocytes, induced by palmitate; implications for Alzheimer's Disease

NEUROBIOLOGY OF AGING

卷:35

Article

Liu, Li¹  Chan, Christina^2,3 

[1] Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA

[2] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA

[3] Michigan State Univ, Dept Chem Engn & Mat Sci, E Lansing, MI 48824 USA

关键词: Alzheimer's disease;    Fatty acid;    Inflammasome;    IL-1 beta;    IPAF;   

DOI  :  10.1016/j.neurobiolaging.2013.08.016

来源: Elsevier

【 摘 要 】

Inflammatory response has been strongly implicated in the pathogenesis of numerous diseases, including Alzheimer's disease (AD). However, little is known about the molecular mechanisms initiating the generation of inflammatory molecules in the central nervous system, such as interleukin-1 beta (IL-1 beta). Previously we identified that palmitate can induce primary astrocytes to produce cytokines, causing AD-like changes in primary neurons. Here we investigated and identified that palmitate induced the activation of ice protease-activating factor (IPAF) eapoptosis-associated speck-like protein containing a caspase activation and recruitment domains (CARD) (ASC) inflammasome in astrocytes leading to the maturation of IL-1 beta, thereby implicating that not only pathogen-related factors can activate the IPAF-ASC inflammasome. Moreover, downregulating IPAF (which was found to be regulated by cAMP response element-binding protein) in astrocytes through silencing to decrease IL-1 beta secretion from the astrocytes reduced the generation of amyloid-beta(42) by primary neurons. Furthermore, the expression levels of IPAF and ASC were found significantly elevated in a subgroup of sporadic AD patients, suggesting an involvement of the IPAF-ASC inflammasome in the inflammatory response associated with AD, and thus could be a potential therapeutic target for AD. (C) 2014 Elsevier Inc. All rights reserved.

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