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Review
. 2019 Dec;25(12):1299-1307.
doi: 10.1111/cns.13262. Epub 2019 Nov 14.

Update of inflammasome activation in microglia/macrophage in aging and aging-related disease

Meng-Yan Hu  1 , Yin-Yao Lin  1 , Bing-Jun Zhang  1 , Dan-Li Lu  1 , Zheng-Qi Lu  1 , Wei Cai  1   2
Affiliations
Review

Update of inflammasome activation in microglia/macrophage in aging and aging-related disease

Meng-Yan Hu et al. CNS Neurosci Ther. 2019 Dec.

Abstract

Aging and aging-related CNS diseases are associated with inflammatory status. As an efficient amplifier of immune responses, inflammasome is activated and played detrimental role in aging and aging-related CNS diseases. Macrophage and microglia display robust inflammasome activation in infectious and sterile inflammation. This review discussed the impact of inflammasome activation in microglia/macrophage on senescence "inflammaging" and aging-related CNS diseases. The preventive or therapeutic effects of targeting inflammasome on retarding aging process or tackling aging-related diseases are also discussed.

Keywords: aging; inflammasome; inflammation; macrophage; microglia.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Two‐signal model of inflammasome signaling. The classic understanding of inflammasome is based on a two‐signal model. In signal 1, sensors (eg, NLRP3) of inflammasome are activated by PAMPs/ DAMPs, leading to activation of NF‐κB pathway and increased transcription of inflammasome‐relevant genes such as NLRP3 and pro‐IL1β. In signal 2, PAMPs/DAMPs (eg, ATP) further activate the inflammasome sensors. The sensors then undergo oligomerization and attach to ASC. ASC acts as a molecular platform that recruits pro‐caspase enzymes. The pro‐caspase enzymes are then cleaved into their active form which subsequently cleave pro‐IL1β and pro‐IL18 into cleaved‐IL1β and cleaved‐IL18
Figure 2
Figure 2
Inflammasome activation inhibits autophagy during aging. Autophagy can negatively regulate inflammasome activation by removing mitochondria‐derived stimuli. Aging impaired fusion of lysosomes with autophagosome, resulting in inflammasome activation by mitochondrial DNA (mtDNA) and ROS efflux from impaired mitochondria
Figure 3
Figure 3
Vicious circle form between Aβ deposition and NLRP3 inflammasome activation in microglia/macrophage during AD. Inflammasome is activated in microglia/macrophage by Aβ directly, or by lysosomal damage and ROS production resulted from Aβ deposition. On the other hand, activation of inflammasome promotes Aβ aggregation exacerbating AD pathology
Figure 4
Figure 4
Interactions of inflammasome in microphage with neural inflammation and aging‐related diseases. Inflammasome activation in microglia/macrophage could be triggered by Aβ plague deposition and tau neurofibrillary tangle in AD, α‐synuclein in PD, and neurons necroptosis in CNS stroke. Therefore, inflammasome activation is one of the consequences of CNS disease development. On the other hand, inflammasome activation exacerbates to neural inflammation, which plays detrimental role in neurodegenerative diseases and CNS stroke. Thus, inflammasome activation is one of the reasons for CNS disease progression
See this image and copyright information in PMC

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