Review Report on NLRP3 Target / Biomarker Content of Review Report on NLRP3 Target / Biomarker
NLRP3
Other Name(s): Muckle-Wells syndrome | OTTHUMP00000230825 | Cold-induced autoinflammatory syndrome 1 protein | NACHT, LRR and PYD containing protein 3 | OTTHUMP00000038410 | NLR family pyrin domain containing 3, transcript variant 2 | MWS | PYPAF1 | CLR1.1 | NLRP3 variant 6 | Cryopyrin | Nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 | NACHT domain-, leucine-rich repeat-, and PYD-containing protein 3 | Angiotensin/vasopressin receptor AII/AVP-like | cold autoinflammatory syndrome 1 protein | cold-induced autoinflammatory syndrome 1 protein | AII/AVP | DFNA34 | LRR and PYD containing protein 3 | cryopyrin | NALP3 | FCU | NLR family pyrin domain containing 3, transcript variant 5 | caterpiller protein 1.1 | PYRIN-containing APAF1-like protein 1 | KEFH | cryopyrin, NACHT, LRR and PYD domains - containing protein 3 | NACHT, LRR and PYD domains-containing protein 3 (isoform a) | NACHT, LRR and PYD domains-containing protein 3 isoform b | Cold autoinflammatory syndrome 1 protein | nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 | CIAS1 | NACHT, LRR and PYD domains-containing protein 3 (isoform c) | NACHT, LRR and PYD domains-containing protein 3 isoform d | OTTHUMP00000038409 | OTTHUMP00000038411 | AII | NACHT, LRR and PYD domains-containing protein 3 isoform e | AVP | NLR family pyrin domain containing 3, transcript variant 3 | NLPR3 | NLR family pyrin domain containing 3 | NACHT, LRR and PYD domains-containing protein 3 | NLR family pyrin domain containing 3, transcript variant 4 | Chromosome 1 open reading frame 7 | autosomal dominant 34 | FCAS1 | NACHT | FCAS | AGTAVPRL | deafness | FLJ95925 | NACHT, LRR and PYD domains-containing protein 3 (isoform e) | NLRP3 variant 2 | NLRP3 variant 5 | NLRP3 variant 1 | NLR family pyrin domain containing 3, transcript variant 6 | NLRP3 variant 3 | Caterpiller protein 1.1 | OTTHUMP00000038408 | deafness, autosomal dominant 34 | NLR family pyrin domain containing 3, transcript variant 1 | NLRP3 variant 4 | C1orf7 | NLRP3_HUMAN

Drug Target and Biomarker: NLRP3

Glucocorticoid resistance: Patients with idiopathic nephrotic syndrome (INS) may develop resistance to glucocorticoids (GCs) due to epigenetic changes in the NLRP3 gene. This mechanism is related to leukocyte epigenetic changes and may contribute to the development of resistance to GCs in INS patients.

Inflammasome activation: NLRP3 plays a crucial role in both canonical and non-canonical inflammasome activation pathways. Gram-negative bacteria can activate the NLRP3 inflammasome, leading to the release of IL-1beta/IL-18 and pyroptosis. In human monocytes, an alternative NLRP3 inflammasome pathway is activated in response to LPS.

Two-signal model for NLRP3 inflammasome activation: The activation of the NLRP3 inflammasome involves two signals: priming and activation. Priming, which is induced by microbial or endogenous molecules, upregulates NLRP3 expression. Activation occurs through various stimuli like ATP, pore-forming toxins, viral RNA, and particulate matter. K+ efflux, Ca2+ signaling, reactive oxygen species (ROS), mitochondrial dysfunction, and lysosomal rupture are proposed triggers for NLRP3 activation.

Post-translational modifications and regulators of NLRP3: NLRP3 is regulated by post-translational modifications such as phosphorylation, ubiquitination, sumoylation, and S-nitrosylation. These modifications can either positively or negatively affect NLRP3 activation. Additionally, NLRP3 interacts with various proteins and molecules, including ARIH2, BRCC3, FBX12, JNK1, and SENP6/7.

Autophagy and NLRP3: Autophagy plays a role in NLRP3 regulation. Under stress conditions, defective autophagy can lead to the accumulation of damaged mitochondria and activation of the NLRP3 inflammasome, resulting in increased production of IL-1beta and inflammation. On the other hand, p62, an adaptor protein, can stimulate the removal of damaged mitochondria, inhibiting inflammasome activation and pro-inflammatory IL-1beta synthesis.

Overall, NLRP3 is involved in glucocorticoid resistance, inflammasome activation, and various post-translational modifications. Its modulation and regulation are crucial in the context of immune responses and inflammatory processes.
- NLRP3 expression is regulated by various transcription factors, including NF-kappaB, GFI1, AhR, NR1D1, and NFAT5.
- NLRP3 inflammasome priming is mediated by post-translational modifications independent of transcription.
- Classical activation of the NLRP3 inflammasome involves a two-step model, with signal 1 upregulating NLRP3 expression and signal 2 detecting cellular integrity perturbations.
- Alternative inflammasome activation can be triggered by a single signal, such as LPS or an iNKT cell derived signal.
- Increased sarcoplasmic reticulum (SR) Ca2+ leak and spontaneous SR Ca2+-release events can lead to NLRP3 inflammasome activation.
- Various stimuli, including PAMPs and DAMPs, trigger upstream signaling pathways that converge to activate the NLRP3 inflammasome.
- The EPEC pathogen subverts NLRP3 inflammasome assembly through the effector NleA, which inhibits NLRP3 activation and association with ASC.
- The NLRP3 inflammasome pathway can be involved in epithelial mesenchymal transition (EMT), potentially promoting the EMT process.

Overall, NLRP3 expression and activation are regulated by various transcription factors and signaling pathways, and it plays a role in inflammatory responses, cellular integrity, and EMT processes.

Protein Name: NLR Family Pyrin Domain Containing 3

Functions: Sensor component of the NLRP3 inflammasome, which mediates inflammasome activation in response to defects in membrane integrity, leading to secretion of inflammatory cytokines IL1B and IL18 and pyroptosis (PubMed:16407889, PubMed:18604214, PubMed:18403674, PubMed:23582325, PubMed:28847925, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:27929086, PubMed:28656979, PubMed:25686105, PubMed:30487600, PubMed:30612879, PubMed:31086327, PubMed:31086329, PubMed:31189953, PubMed:34512673, PubMed:36442502). In response to pathogens and other damage-associated signals that affect the integrity of membranes, initiates the formation of the inflammasome polymeric complex composed of NLRP3, CASP1 and PYCARD/ASC (PubMed:16407889, PubMed:18403674, PubMed:28847925, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:27432880, PubMed:31189953, PubMed:36142182, PubMed:36442502). Recruitment of pro-caspase-1 (proCASP1) to the NLRP3 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion and pyroptosis (PubMed:23582325, PubMed:28847925, PubMed:33231615, PubMed:34133077, PubMed:34341353, PubMed:31189953). Activation of NLRP3 inflammasome is also required for HMGB1 secretion; stimulating inflammatory responses (PubMed:22801494). Under resting conditions, ADP-bound NLRP3 is autoinhibited (PubMed:35114687). NLRP3 activation stimuli include extracellular ATP, nigericin, reactive oxygen species, crystals of monosodium urate or cholesterol, amyloid-beta fibers, environmental or industrial particles and nanoparticles, such as asbestos, silica, aluminum salts, cytosolic dsRNA, etc (PubMed:16407889, PubMed:18604214, PubMed:18403674, PubMed:19414800, PubMed:23871209). Almost all stimuli trigger intracellular K(+) efflux (By similarity). These stimuli lead to membrane perturbation and activation of NLRP3 (By similarity). Upon activation, NLRP3 is transported to microtubule organizing center (MTOC), where it is unlocked by NEK7, leading to its relocalization to dispersed trans-Golgi network (dTGN) vesicle membranes and formation of an active inflammasome complex (PubMed:36442502). Associates with dTGN vesicle membranes by binding to phosphatidylinositol 4-phosphate (PtdIns4P) (PubMed:30487600, PubMed:34554188). Shows ATPase activity (PubMed:17483456)

The "NLRP3 Target / Biomarker Review Report" is a customizable review of hundreds up to thousends of related scientific research literature by AI technology, covering specific information about NLRP3 comprehensively, including but not limited to:
•   general information;
•   protein structure and compound binding;
•   protein biological mechanisms;
•   its importance;
•   the target screening and validation;
•   expression level;
•   disease relevance;
•   drug resistance;
•   related combination drugs;
•   pharmacochemistry experiments;
•   related patent analysis;
•   advantages and risks of development, etc.
The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

More Common Targets

NLRP3 Inflammasome | NLRP3P1 | NLRP4 | NLRP5 | NLRP6 | NLRP7 | NLRP8 | NLRP9 | NLRP9P1 | NLRX1 | NMB | NMBR | NMD3 | NMDA receptor | NME1 | NME1-NME2 | NME2 | NME2P1 | NME3 | NME4 | NME5 | NME6 | NME7 | NME8 | NME9 | NMI | NMNAT1 | NMNAT2 | NMNAT3 | NMRAL1 | NMRAL2P | NMRK1 | NMRK2 | NMS | NMT1 | NMT2 | NMTRQ-TTG10-1 | NMTRQ-TTG12-1 | NMTRV-TAC1-1 | NMU | NMUR1 | NMUR2 | NNAT | NNMT | NNT | NNT-AS1 | NOA1 | NOB1 | NOBOX | NOC2L | NOC2LP2 | NOC3L | NOC4L | NOCT | NOD1 | NOD2 | NODAL | NOG | NOL10 | NOL11 | NOL12 | NOL3 | NOL4 | NOL4L | NOL4L-DT | NOL6 | NOL7 | NOL8 | NOL9 | NOLC1 | NOM1 | NOMO1 | NOMO2 | NOMO3 | Non-protein coding RNA 185 | NONO | NOP10 | NOP14 | NOP14-AS1 | NOP16 | NOP2 | NOP53 | NOP56 | Nop56p-associated pre-rRNA complex | NOP58 | NOP9 | NOPCHAP1 | NORAD | NOS1 | NOS1AP | NOS2 | NOS2P1 | NOS2P2 | NOS2P3 | NOS3 | NOSIP | NOSTRIN | Notch ligands | Notch receptor | Notch Transcriptional Activation Complex