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Inflammasomes: mechanism of action, role in disease, and therapeutics

Abstract

The inflammasomes are innate immune system receptors and sensors that regulate the activation of caspase-1 and induce inflammation in response to infectious microbes and molecules derived from host proteins. They have been implicated in a host of inflammatory disorders. Recent developments have greatly enhanced our understanding of the molecular mechanisms by which different inflammasomes are activated. Additionally, increasing evidence in mouse models, supported by human data, strongly implicates an involvement of the inflammasome in the initiation or progression of diseases with a high impact on public health, such as metabolic disorders and neurodegenerative diseases. Finally, recent developments pointing toward promising therapeutics that target inflammasome activity in inflammatory diseases have been reported. This review will focus on these three areas of inflammasome research.

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Figure 1: Mechanisms of NLRP3 inflammasome activation.
Figure 2: Mechanisms of NLRC4, AIM2 and noncanonical NLRP3 inflammasome activation.
Figure 3: Mechanisms of NLRP3 inflammasome action in Alzheimer's disease.
Figure 4: Mechanism of inflammasome activation in inflammatory disease.

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Acknowledgements

This work was supported by US National Institutes of Health grants R37-AI029564 and CA156330 and National Multiple Sclerosis Society grant 1785G9/2 awarded to J.P.-Y.T.

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Correspondence to Jenny P-Y Ting.

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Guo, H., Callaway, J. & Ting, JY. Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 21, 677–687 (2015). https://doi.org/10.1038/nm.3893

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