**3.1 Description of an inflammasome**

Inflammation is amplified and maintained by the activities of pro-inflammatory cytokines principally IL-1β and IL-18. However, the previously described inflammatory mechanism leads to the formation of these cytokines in an inactive form. In this part, we focus on the analysis of the molecular platform implicated in the activation of these cytokines called inflammasome. An inflammasome is an innate immune complex that recognizes pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) and leads to the activation of an inflammatory caspase: caspase-1 [20]. It is a macromolecule complex formed by oligomerization of a specific type pattern recognition receptor, an adaptor protein and caspase-1. This association results from the interaction between homotypic domains [20]. Pattern recognition receptors (PRRs) implicated in the inflammasome's structure are particular. Their activation leads specifically to the activation of caspase-1 rather than the activation of transcription factors such as nuclear factor kappa-B (NF-κB) or IFN regulatory factor 3/7 (IRF3/7) as well as protein synthesis [20]. Three receptors' families are actually descripted as principal activators of the inflammasome: nucleotide-binding domain and leucine-rich repeats containing receptors (NLR), AIM2 {absent in melanoma 2}-like receptors (ALR), and RIG {retinoic acid inducible gene}-I-like receptor (RLR) [20]. The implication of the RLR in the activation of inflammasome is still debated.

Twenty-two NLR types have been identified in humans. They have a structural organization with a leucine-rich repeat (LRR) domain, which interacts with the ligand; a nucleotide-binding domain (NBD), which permits the ATP depending oligomerization of NLR into an hexameric form that activates the inflammasome; and an effector domain, which permits the transduction of signals (**Figure 3**) [21]. The effector domain is different for each NLR receptors and aids in their distinction. The NLRP have as effector domain the pyrin domain (PYD); the NLRC have as

**Figure 3.**

*Inflammasome structure (modified from [20]) (A) structure of Inflammasome domains (B) NLRP3 Inflammasome. \*Apoptosis-associated speck-like protein containing a CARD plays the role of adaptor protein.*

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**Table 1.**

*Major Inflammasome activators (modified from [20]).*

*Neuroprotection: The Way of Anti-Inflammatory Agents DOI: http://dx.doi.org/10.5772/intechopen.90509*

extremity is formed by a pyrin domain [20].

**3.2 Activation of the inflammasome**

effector domain the caspase activation and recruitment domain (CARD); and the NLRB or NAIP (NLR family apoptosis inhibitory protein) have as effector domain the baculoviral inhibitor of apoptosis protein repeat (BIR) [21]. AIM2-like receptors (ALR) are formed by four receptors: the AIM2, interferon-γ- inducible antigen 16 (IFI16), myeloid cell nuclear differentiation antigen (MNDA), and interferoninducible protein X (IFIX). The end carboxyl extremity of these receptors is formed by an HIN200 domain which reacts with double-stranded DNA, and the end amino

Activation of inflammasome requires the interaction between its receptors and the specific ligands grouped in the name of pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) [11, 12]. A large number of inflammasome ligands have been identified; the major ones are presented in **Table 1**. Receptors implicated in the inflammasome structure are located on the intracellular site of cell membrane. This localization means that the inflammasome's receptors are activated by ligands present on the inner aspect of the cell [20]. In other words, an inflammasome is activated in a cell only if the considered cell is infected, mutated, or damaged. The most studied inflammasome platform is the NLRP3 or cryopirine; its activation can be mediated by a double stimulus. The first is the stimulation of a toll-like receptor (TLR) which leads to the activation of the transcription pathway of pro-IL-1β that raises the transcription of the genes of NLRP3 and its deubiquitination [22]. The second stimulus is

**Receptors Stimuli DAMPs/PAMPs**

Myramyl dipeptide of peptidoglycan bacterial wall PAMP

Reactive oxygen species DAMP Asbestos fiber DAMP Potassium ions efflux DAMP Urate crystal DAMP Silica crystal DAMP Aluminum salt DAMP Cholesterol crystal DAMP β-amyloid protein DAMP Pore forming bacteria toxin PAMP

NLRP1 Anthrax toxin PAMP

NLRP3 Extracellular ATP DAMP

NLRP6 Unknown Unknown NLRP7 Bacteria lipopeptide PAMP NLRP12 *Yersinia pestis* unknown pattern PAMP NLRC4 Flagellin PAMP

AIM2 Bacterial and viral DNA PAMP IFI16 Viral nuclear DNA PAMP

Type 3 and 4 secretion system PAMP

*Neuroprotection: The Way of Anti-Inflammatory Agents DOI: http://dx.doi.org/10.5772/intechopen.90509*

*Neuroprotection - New Approaches and Prospects*

**3. Inflammasome molecular platform**

RLR in the activation of inflammasome is still debated.

Inflammation is amplified and maintained by the activities of pro-inflammatory cytokines principally IL-1β and IL-18. However, the previously described inflammatory mechanism leads to the formation of these cytokines in an inactive form. In this part, we focus on the analysis of the molecular platform implicated in the activation of these cytokines called inflammasome. An inflammasome is an innate immune complex that recognizes pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) and leads to the activation of an inflammatory caspase: caspase-1 [20]. It is a macromolecule complex formed by oligomerization of a specific type pattern recognition receptor, an adaptor protein and caspase-1. This association results from the interaction between homotypic domains [20]. Pattern recognition receptors (PRRs) implicated in the inflammasome's structure are particular. Their activation leads specifically to the activation of caspase-1 rather than the activation of transcription factors such as nuclear factor kappa-B (NF-κB) or IFN regulatory factor 3/7 (IRF3/7) as well as protein synthesis [20]. Three receptors' families are actually descripted as principal activators of the inflammasome: nucleotide-binding domain and leucine-rich repeats containing receptors (NLR), AIM2 {absent in melanoma 2}-like receptors (ALR), and RIG {retinoic acid inducible gene}-I-like receptor (RLR) [20]. The implication of the

Twenty-two NLR types have been identified in humans. They have a structural organization with a leucine-rich repeat (LRR) domain, which interacts with the ligand; a nucleotide-binding domain (NBD), which permits the ATP depending oligomerization of NLR into an hexameric form that activates the inflammasome; and an effector domain, which permits the transduction of signals (**Figure 3**) [21]. The effector domain is different for each NLR receptors and aids in their distinction. The NLRP have as effector domain the pyrin domain (PYD); the NLRC have as

*Inflammasome structure (modified from [20]) (A) structure of Inflammasome domains (B) NLRP3 Inflammasome. \*Apoptosis-associated speck-like protein containing a CARD plays the role of adaptor protein.*

**3.1 Description of an inflammasome**

**324**

**Figure 3.**

effector domain the caspase activation and recruitment domain (CARD); and the NLRB or NAIP (NLR family apoptosis inhibitory protein) have as effector domain the baculoviral inhibitor of apoptosis protein repeat (BIR) [21]. AIM2-like receptors (ALR) are formed by four receptors: the AIM2, interferon-γ- inducible antigen 16 (IFI16), myeloid cell nuclear differentiation antigen (MNDA), and interferoninducible protein X (IFIX). The end carboxyl extremity of these receptors is formed by an HIN200 domain which reacts with double-stranded DNA, and the end amino extremity is formed by a pyrin domain [20].
