complex(GO:"NLRP3 inflammasome complex")
NLRP3 inflammasome activation results from TLR ligation and concomitant uptake of Ab in models of AD PubMed:28019679
Using a similar mouse model, Shi et al. treated animals with the antimalarial drug artemisinin, showing that this treatment results in inhibition of NFkB and presumably the NLRP3 inflammasome (13) PubMed:28019679
Using the herbizide, N,N0-dimethyl-4,40-bipyridinium dichloride (paraquat) as a mitochondrial toxin, which is known to induce oxidative stress, Chen et al. found increased levels of caspase-1 and IL-1b in brain of wild type and APP/PS1 transgenic mice (2), suggesting that those were due to NLRP3 inflammasome activation PubMed:28019679
Activation of the NLRP3 inflammasome by fibrillar Abeta has been described first by Halle et al. in 2008 PubMed:28019679
NLRP3 inflammasome activation results from TLR ligation and concomitant uptake of Ab in models of AD PubMed:28019679
One of the canonical pathways of this innate immune response evoked by Abeta is the activation of the NOD-like receptor (NLR) family, pyrin domain containing 3 (NLRP3) inflammasome that became a focus of intense research PubMed:28019679
Soluble Abeta (sAbeta)-induces NLRP3 inflammasome activation, however it requires the presence of the surface receptor CD36 (12) PubMed:28019679
NLRP3 activation was characterized by ASC speck formation in an immune-activated microglial cell line and required a dual signal to become effective: the phagocytic uptake of Abeta and cathepsin B release after lysosomal disruption PubMed:28019679
The combined effect of the increased IDE production and phagocytic Abeta clearance reduced the cerebral Abeta load substantially, even at late life. Since immunohistochemistry found NLRP3 exclusively expressed in microglial cells, it has been concluded that the observed changes were entirely due to NLRP3 inflammasome modulation in these cells PubMed:28019679
A few molecules, such as amyloid-β, can induce both NLRP3 priming through TLR activation and NLRP3 inflammasome activation68. PubMed:23702978
Similarly, activation of the NLRP1B and NLRP3 inflammasomes depends on low K+ concentrations in intracellular compartments79, and a low K+ concentration promotes the assembly of the ASC speck6. PubMed:23702978
IFNs upregulate AIM2 expression but they downregulate IL-1β expression and inhibit the NLRP3 inflammasome. PubMed:23702978
Thus, it is not surprising that effector and memory CD4+ T cells have the capacity to inhibit the activation of the NLRP1 and NLRP3 inflammasomes in a contact-dependent manner, possibly via TNFR superfamily molecules such as CD40 ligand (CD40L)70. PubMed:23702978
The authors proposed that another, not yet characterized, ER stress pathway activates the NLRP3 inflammasome90. PubMed:23702978
Another regulator of Ca2+, namely C/EPB-homologous protein (CHOP; also known as DDIT3), has been implicated in NLRP3 inflammasome activation89 PubMed:23702978
Phagocytosis and subsequent lysosomal damage trigger by Aβ initiate the activation of the NLRP3 inflammasome in the microglia (Halle et al., 2008) PubMed:24561250
In vivo and cell studies demonstrate that fibrillar Aβ activates the NLRP3 inflammasome which is composed of the NLRP3 receptor, ASC and caspase-1, to produce IL-1β in microglia (Halle et al., 2008) PubMed:24561250
Phagocytosis and subsequent lysosomal damage trigger by Aβ initiate the activation of the NLRP3 inflammasome in the microglia (Halle et al., 2008) PubMed:24561250
As for the NLRP1 and NLRP3 inflammasomes, the oligomerzied NLRs recruit and interact with the adaptor protein ASC, which in turn recruits the effector protein procaspase-1 that is central to the activation of inflammasomes (Huang et al., 2013) PubMed:24561250
In support, a recent study in APP/PS1 mice confirms that the NLRP3 inflammasome contributes to the AD pathology (Heneka et al., 2013) PubMed:24561250
Of these, the NLRP3 inflammasome can be acti- vated via bacterial RNA species [3]. PubMed:27314526
P2X7 expressed by microglial cells will also activate the NLP3 inflammasome [30, 32] and the expression of P2X7 is likely to be increased in AD brains [35]. PubMed:27314526
Activation of NLRP3 leads to the generation of interleukin-1b (IL-1b) and interleukin 18 (IL-18), which are being cleaved by caspase-1 from their inactive precursors and subsequently PubMed:28019679
Activation of NLRP3 leads to the generation of interleukin-1b (IL-1b) and interleukin 18 (IL-18), which are being cleaved by caspase-1 from their inactive precursors and subsequently PubMed:28019679
Using the herbizide, N,N0-dimethyl-4,40-bipyridinium dichloride (paraquat) as a mitochondrial toxin, which is known to induce oxidative stress, Chen et al. found increased levels of caspase-1 and IL-1b in brain of wild type and APP/PS1 transgenic mice (2), suggesting that those were due to NLRP3 inflammasome activation PubMed:28019679
NLRP3 inflammasome formation and subsequent activation of caspase-1 cleavage capacity was instrumental for Abeta-induced nitric oxide production and TNF-a release PubMed:28019679
Using the herbizide, N,N0-dimethyl-4,40-bipyridinium dichloride (paraquat) as a mitochondrial toxin, which is known to induce oxidative stress, Chen et al. found increased levels of caspase-1 and IL-1b in brain of wild type and APP/PS1 transgenic mice (2), suggesting that those were due to NLRP3 inflammasome activation PubMed:28019679
NLRP3 inflammasome formation and subsequent activation of caspase-1 cleavage capacity was instrumental for Abeta-induced nitric oxide production and TNF-a release PubMed:28019679
NLRP3 inflammasome formation and subsequent activation of caspase-1 cleavage capacity was instrumental for Abeta-induced nitric oxide production and TNF-a release PubMed:28019679
This finding was associated with spatial memory dysfunction and an increase in Abeta plaque deposition PubMed:28019679
This finding was associated with spatial memory dysfunction and an increase in Abeta plaque deposition PubMed:28019679
In the CNS, the production of IL-1β by inflammasomes, specifically NLRP1, NLRP2, NLRP3 and NLRC4, is well-characterized as compared to other interleukins (Minkiewicz et al., 2013; Trendelenburg, 2008) PubMed:24561250
In vivo and cell studies demonstrate that fibrillar Aβ activates the NLRP3 inflammasome which is composed of the NLRP3 receptor, ASC and caspase-1, to produce IL-1β in microglia (Halle et al., 2008) PubMed:24561250
In support, a recent study in APP/PS1 mice confirms that the NLRP3 inflammasome contributes to the AD pathology (Heneka et al., 2013) PubMed:24561250
Similarly, inhibiting the NLRP3 inflammasome reduces the neuritic plaque burden in an AD transgenic mouse model (Shi et al., 2013) PubMed:24561250
The NLRP3 inflammasome has a role in AD by increas- ing caspase-1 expression levels in AD brains [13, 23]. PubMed:27314526
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