p(HGNC:CASP1)
MB is a phenothiazine that crosses the blood brain barrier and acts as a redox cycler. Moreover, besides its beneficial properties as being able to improve energy metabolism and to act as an antioxidant, it is also able to reduce tau protein aggregation PubMed:26751493
Further data, showing “neuronal pyroptosis” of Abeta exposed neurons in a NLRP1- dependent and caspase-1-mediated manner may point to a vicious cycle, by which NLRP1 is causing neurodegeneration in response to increased Abeta production (14) 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
Recently, Kaushal et al. described the involvement of NLRP1 inflammasome activation in neurons. In these experiments, serum deprivation induced NLRP1-dependent caspase-1 activity and ASC speck formation, which resulted in caspase-6 activation and an increase in the Ab42/total Ab ratio (11) 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
NLRC4 and NLRP1 can both activate caspase 1 through their CARDs without recruiting ASC; however, the recruitment of ASC greatly enhances the formation of the complex and the processing of IL-1β7,13–16. PubMed:23702978
NLRC4 and NLRP1 can both activate caspase 1 through their CARDs without recruiting ASC; however, the recruitment of ASC greatly enhances the formation of the complex and the processing of IL-1β7,13–16. PubMed:23702978
Once the protein complexes have formed, the inflammasomes activate caspase 1, which proteolytically activates the pro-inflammatory cytokines interleukin-1β (IL-1β)3 and IL-18. PubMed:23702978
Indeed, inflammasomes (which induce pyroptosis through caspase 1 or caspase 11 activation) and apoptosomes (which activate caspase 9 in response to cytochrome c release from mitochondria) are two mechanisms by which compromised cells are eliminated. PubMed:23702978
Using its CARD, ASC brings monomers of procaspase 1 into close proximity, which initiates caspase 1 self- cleavage and the formation of the active heterotetrameric caspase 1. PubMed:23702978
NLRC4 and NLRP1 can both activate caspase 1 through their CARDs without recruiting ASC; however, the recruitment of ASC greatly enhances the formation of the complex and the processing of IL-1β7,13–16. PubMed:23702978
Similarly, mouse caspase 12, which is a paralogue of caspase 1, interacts with caspase 1 to reduce its activity110 PubMed:23702978
NLRC4 and NLRP1 can both activate caspase 1 through their CARDs without recruiting ASC; however, the recruitment of ASC greatly enhances the formation of the complex and the processing of IL-1β7,13–16. PubMed:23702978
CARD-only proteins (COPs) can also inhibit caspase 1 activation112. CARD18 (also known as ICEBERG) and CARD16 (also known as pseudoICE and COP1) were the first ‘decoy’ COPs to be described113. PubMed:23702978
CARD-only proteins (COPs) can also inhibit caspase 1 activation112. CARD18 (also known as ICEBERG) and CARD16 (also known as pseudoICE and COP1) were the first ‘decoy’ COPs to be described113. PubMed:23702978
By contrast, nitrosylation of caspase 9 inhibits its function94. Similarly, caspase 1 can be inhibited by nitrosylation95, which suggests that modification by reactive molecules is a general mechanism for the regulation of caspase activity. PubMed:23702978
The formation of this complex activates RIP3, which is necessary for the cleavage of pro-IL-1β by both the NLRP3-caspase 1 and the caspase 8 pathways56 (FIG. 1). PubMed:23702978
Like IL-1β, in most cases, the mature secretable form of IL-18 is generated by caspase-1 through the activation of inflammasome PubMed:24561250
ATP, a danger-associated molecular pattern that is released from damaged cells after brain injury, activates the NLRP2 inflammasome, which consists of the NLRP2 receptor, ASC and caspase-1, in human astrocytes (Minkiewicz 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
Post activation of the inflammasome, caspase 1 enzyme initiates the maturation of pro-inflammatory cytokines particularly interleukin (IL)-1beta, IL-18, and IL-33 [4] (Fig. 1),and inflammation mediated cell death occurs via the nucleotide-binding domain and leucine-rich repeat(NLR) family of proteins [5]. PubMed:27314526
Both IL-1 beta and IL-18 are generated in their mature secreted form by caspase-1 through activa- tion of the inflammasome. PubMed:27314526
In the NLRP3 inflammasome, the NLR pro- tein recruits the inflammasome-adaptor protein apoptosis-associated speck-like protein containing CARD (ASC), which in turn interacts with caspase- 1 leading to its activation [7]. PubMed:27314526
In AD, microglial cells and astrocytes express NLRP3, which in turn can detect A beta plaques and act by secreting caspase-1 to activate IL-1 beta and IL- 18 [23–25]. PubMed:27314526
As a component of inflammasome, NLRP3 is the best characterized member of NLRs, which recruits and activates caspase-1 via the adapter molecule ASC (apoptosis- associated speck-like protein containing caspase activation and recruitment domain) [8, 9]. PubMed:24464629
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
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
Further data, showing “neuronal pyroptosis” of Abeta exposed neurons in a NLRP1- dependent and caspase-1-mediated manner may point to a vicious cycle, by which NLRP1 is causing neurodegeneration in response to increased Abeta production (14) PubMed:28019679
Once the protein complexes have formed, the inflammasomes activate caspase 1, which proteolytically activates the pro-inflammatory cytokines interleukin-1β (IL-1β)3 and IL-18. PubMed:23702978
Active caspase 1 proteolytically activates a number of proteins8, including pro-IL-1β and pro-IL-18 (REFS 9,10), and induces their release via a non-classical secretion pathway11. PubMed:23702978
Active caspase 1 proteolytically activates a number of proteins8, including pro-IL-1β and pro-IL-18 (REFS 9,10), and induces their release via a non-classical secretion pathway11. PubMed:23702978
Caspase 1mediated activation of members of the IL-1β cytokine family leads to the recruitment and the activation of other immune cells, such as neutrophils, at the site of infection and/or tissue damage. PubMed:23702978
Once the protein complexes have formed, the inflammasomes activate caspase 1, which proteolytically activates the pro-inflammatory cytokines interleukin-1β (IL-1β)3 and IL-18. PubMed:23702978
Active caspase 1 proteolytically activates a number of proteins8, including pro-IL-1β and pro-IL-18 (REFS 9,10), and induces their release via a non-classical secretion pathway11. PubMed:23702978
Active caspase 1 proteolytically activates a number of proteins8, including pro-IL-1β and pro-IL-18 (REFS 9,10), and induces their release via a non-classical secretion pathway11. PubMed:23702978
Indeed, inflammasomes (which induce pyroptosis through caspase 1 or caspase 11 activation) and apoptosomes (which activate caspase 9 in response to cytochrome c release from mitochondria) are two mechanisms by which compromised cells are eliminated. PubMed:23702978
Caspase-1 is the protease that cleaves the precursor of the proinflammatory molecules to form their mature form, such as IL-1β and IL-18 (Schroder and Tschopp, 2010) PubMed:24561250
Caspase-1 is the protease that cleaves the precursor of the proinflammatory molecules to form their mature form, such as IL-1β and IL-18 (Schroder and Tschopp, 2010) PubMed:24561250
Like IL-1β, in most cases, the mature secretable form of IL-18 is generated by caspase-1 through the activation of inflammasome PubMed:24561250
ATP, a danger-associated molecular pattern that is released from damaged cells after brain injury, activates the NLRP2 inflammasome, which consists of the NLRP2 receptor, ASC and caspase-1, in human astrocytes (Minkiewicz et al., 2013) PubMed:24561250
Post activation of the inflammasome, caspase 1 enzyme initiates the maturation of pro-inflammatory cytokines particularly interleukin (IL)-1beta, IL-18, and IL-33 [4] (Fig. 1),and inflammation mediated cell death occurs via the nucleotide-binding domain and leucine-rich repeat(NLR) family of proteins [5]. PubMed:27314526
Post activation of the inflammasome, caspase 1 enzyme initiates the maturation of pro-inflammatory cytokines particularly interleukin (IL)-1beta, IL-18, and IL-33 [4] (Fig. 1),and inflammation mediated cell death occurs via the nucleotide-binding domain and leucine-rich repeat(NLR) family of proteins [5]. PubMed:27314526
In AD, microglial cells and astrocytes express NLRP3, which in turn can detect A beta plaques and act by secreting caspase-1 to activate IL-1 beta and IL- 18 [23–25]. PubMed:27314526
Both IL-1 beta and IL-18 are generated in their mature secreted form by caspase-1 through activa- tion of the inflammasome. PubMed:27314526
Once activated, caspase-1 promotes the maturation of the proin- flammatory cytokines IL-1 beta , IL-18, and IL-33. PubMed:27314526
Post activation of the inflammasome, caspase 1 enzyme initiates the maturation of pro-inflammatory cytokines particularly interleukin (IL)-1beta, IL-18, and IL-33 [4] (Fig. 1),and inflammation mediated cell death occurs via the nucleotide-binding domain and leucine-rich repeat(NLR) family of proteins [5]. PubMed:27314526
In AD, microglial cells and astrocytes express NLRP3, which in turn can detect A beta plaques and act by secreting caspase-1 to activate IL-1 beta and IL- 18 [23–25]. PubMed:27314526
Both IL-1 beta and IL-18 are generated in their mature secreted form by caspase-1 through activa- tion of the inflammasome. PubMed:27314526
Once activated, caspase-1 promotes the maturation of the proin- flammatory cytokines IL-1 beta , IL-18, and IL-33. PubMed:27314526
Once activated, caspase-1 promotes the maturation of the proin- flammatory cytokines IL-1 beta , IL-18, and IL-33. PubMed:27314526
As a component of inflammasome, NLRP3 is the best characterized member of NLRs, which recruits and activates caspase-1 via the adapter molecule ASC (apoptosis- associated speck-like protein containing caspase activation and recruitment domain) [8, 9]. PubMed:24464629
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.