CVD

(Dalekos et al. 1997, PMID 9042815) ↑ (7x vs HC) IL-1b of HBP (d=1.38)

HBP: For the 65-74-year-old age group, the following have high blood pressure: 62.0% of women. (https://www.heart.org/idc/groups/heart-public/@wcm/@sop/)

Signals

PAMP (pathogen-associated molecular patterns)	derived from microorganisms	Eg) LPS, Pam2,3, bacteria, viral RNA	PAMPs and DAMPs bind to pattern recognition receptors cytoplasmic NOD-like receptors (NLRs); intracellular sensors; and endocytic gene of the receptors (RLR); transmembrane C-type lectin receptors and Stimulus signaling I-AhR cell, NLRP3 cells; NF-κB pathway-modulating signals. Cell types expressing pattern recognition receptors include innate immune cells such as macrophages, monocytes, dendritic cells, and mast cells but also non-immune cells such as epithelial cells and fibroblasts among others.
DAMP (Damage-associated molecular patterns)	derived from host cells	Eg) HSP, cytochrome C, HMBG1, a--syn, tau and bb--amyloid

Below figure from Rodriguez-Góme 2020

Figure 1. TLR4 signaling pathways activated in microglia during neuroinflammation. (A) LPS binding to TLR4 triggers sequential activation of caspase-8 and caspase-3 with nuclear translocation of NF-κB and expression of genes involved in inflammatory response. The molecular mechanism triggering activation of caspase-8 is unknown at the moment. LPS can also activate the expression of inflammatory genes by means of (B) the MyD88-dependent pathway or (C) the TIR-domain containing adapter-inducing interferon-γ (TRIF)-dependent pathway with receptor-interacting protein kinase 1 (RIPK1) ubiquitination. (D) Although not clearly defined in microglia, under deubiquitinating conditions, RIPK1 can form a ripoptosome-like complex that ultimately leads to necrosome formation and necroptotic cell death with release of DAMPs. (E) TLR4-mediated increase in gene expression of NOD-, LRR- and pyrin domain-containing protein (NLRP3), pro-IL-1β, and pro-IL-18 is the priming stage of inflammasome formation. In the activation stage, the assembly of inflammasome complex activates caspase-1, which allows the maturation of IL-1β and IL-18 and their release through pyroptosis. (F) A noncanonical inflammasome has been also described in microglia that gives rise to caspase-8 activation and IL-1β maturation and release.

Inflammasome

Definition: a multiprotein complex in the microglia plasma,

Function: that function as intracellular sensors of environmental and cellular stress (14-18)

Subtype of inflammasome: here are up to 15 types of inflammasomes (though only eight are well established, each responding to a unique danger signal.

		Components
NLRP3 inflammasome	Most well known	NLRP3 (sensor 이지) receptor protein, THIS is one type of pattern recognition receptor) ASC (apoptosis-associated speck-like protein containing a caspase activating recruitment domain) (downstream Adaptor) caspase-1 (Effector)
Inflammasome cellular schematic showing PAMP/DAMP signal → sensor (NLRP3) → ASC adaptor → caspase-1 effector → IL-1β / IL-18 maturation and pyroptosis.
(Anderson, 2021 #1266) VARIOUS cell types ( neuron, monocyte, macrophage, endothelial cells) can release NLRP3-inflammasome-related EV
NLRP1 inflammasome
NLRC4 inflammasome
AIM2 inflammasome

In vitro model of neuroinflammation

		Human	Mice	rat
Cell line		THP-1: (peripheral) monocyte 를 represent			(Bosshart, 2016 #850) a spontaneously immortalized monocyte-like cell line, derived from the peripheral blood of a childhood case of acute monocytic leukemia (M5 subtype) [3] Release IL-1 Responsive to LPS (b/c they have CD14, and TLR4, MD2) T-RO6673219 inhibited nigericin-induced formation of ASC with an IC50 of 4 nM It also potently blocked nigericin-induced (LDH) release with an IC50 of 1.7 nM
			J774A.1		Derived from a tumour in a female BALB/c mouse
				?	IC50s of 6 nM
Primary cell	ophagy	PBMC (from whole blood of HV).			MJF WORKSHOP 202108: human PBMCs appear to be relatively good at recapitulating in vivo phenotypes for NLRP3 research
			O	?

Uncertain Spans

location	transcription	uncertainty
TLR4 caption / Rodriguez-Góme 2020	citation reads Rodriguez-Góme 2020; preserved verbatim though the canonical author surname is likely Rodríguez-Gómez.	low confidence on diacritic spelling.
In vitro model / TR-06673219 IC50 entries	the highlighted cells read T-RO6673219 inhibited nigericin-induced formation of ASC with an IC50 of 4 nM and the LDH IC50 of 1.7 nM; preserved verbatim.	low confidence on T-RO vs TRO.