Boster Pathways-> Immunology and Inflammation

Inflammasome Signaling Pathway

Inflammasomes are innate immune system receptors that regulate the activation of capsase - 1 and induce inflammation in response to infectious microbes and molecules derived from host proteins.

Overview of Inflammasome Signaling Pathway

Inflammasomes are cytosolic multiprotein complexes that typically include an upstream sensor protein from the NOD(nucleotide-binding oligomerization domain)-like receptor (NLR) family, an adaptor protein called ASC, and a downstream effector called caspase-1. It's a crucial part of the body's natural defenses.

Inflammasomes are innate immune system receptors that regulate the activation of capsase - 1 and induce inflammation in response to infectious microbes and molecules derived from host proteins. Inflammasomes can respond to a wide range of physiological and pathogenic stimuli and play an important role in clearance of pathogens or damaged cells. Innate immune system is the first line of host defense and the engagement of germline - encoded pattern recognition receptors (PRRs) activate in response to harmful stimuli. Inflammasomes, a multiprotein complex that serves as a scafold for the activation of the central protease in this response, capsase-1. By utilizing certain upstream and downstream events in the assembly and activation process ;researchers are able to access engagements of innate immune response.

Inflammation is a natural element of the healing process. Inflammation is triggered by the protein-based molecular machine inflammasome in response to cellular stress, tissue injury, or various signals from pathogenic pathogens. Activation of the inflammasome in peripheral immune cells serves as a regulating function in the production of pyroptotic cell death to remove the harmful immune cell.

Mechanism of Inflammasome Signaling Pathway

The development of inflammasomes is begun by NLR proteins such as NLRP1, NLRP2, NLRP3, NLRP6, NLRP7, NLRC4, and the AIM2 protein, which are activated by a range of PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns) (absent in melanoma-2).

Molecular structure has identified a number of inflammasomes, including NLRP1, NLRP2, NLRP3, NLRC4, and AIM2. The NLRP3 inflammasome is the most studied and well-characterized, consisting of the NLR, the adaptor molecule ASC (poptosis-associated speck-like protein including CARD), and the effector molecule pro-caspase-1. A PYD domain can be found at the N-terminus of NLRP3. It oligomerizes through the NOD domain after activation and attracts ASC via the PYD-PYD interaction with the ASC molecule. NLRP3 has a C-terminal CARD region that can be combined with caspase-1's CARD region (NLRC4 can recruit caspase-1 directly through its N-terminal CARD region). The interaction of these proteins, NLR-PYD-caspase-1, results in the formation of an inflammasome, a large molecular weight protein complex.

Caspase-1 autocleaves as a result of inflammasome formation. Pro-IL-1 and pro-IL-18 are processed by active caspase-1 into their mature and bioactive forms, IL-1 and IL-18. The proinflammatory cytokines IL-1 and IL-18 mature and secrete numerous biological effects that are connected to inflammation, infection, and autoimmune diseases. Pyoptosis can potentially be triggered by inflammasome activation. This impact causes infected cells' cell membranes to perforate in a short amount of time, releasing cytoplasm containing inflammatory factors like IL-1B and IL-18 into the interstitial space, activating the appropriate receptors of nearby cells and producing a larger immune response.

Inflammasome activity has been demonstrated to increase with age in studies, implying that inflammasomes are linked to neuroinflammation during neuronal aging. Psychiatric illnesses such as depression will result from neuronal aging. While neurons produce IL-1 family cytokines, the principal sources of these cytokines in the brain are activated microglia and astrocytes.

A separate set of NLRs, including NLRP1, NLRP3, and NLRC4, activate caspase-1 through the formation of multiprotein complexes known as inflammasomes. Caspases-1 activation regulates the development of the pro-inflammatory cytokines IL-1 and IL-18, as well as pyroptosis. The stimulation of the IL-1 receptor signaling pathway and the nuclear factor kappa B-dependent myeloid differentiation factor (MyD88) results in the transcription of cytokines such IL-8, S100, and macrophage inflammatory protein 2 (MIP2), culminating in a cascade amplification effect.