NLR, the nucleotide-binding domain leucine-rich repeat containing gene family. Curr Opin Immunol

Department of Microbiology-Immunology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, United States.
Current Opinion in Immunology (Impact Factor: 7.87). 03/2008; 20(1):3-9. DOI: 10.1016/j.coi.2008.01.003
Source: PubMed

ABSTRACT The NLR (nucleotide-binding domain leucine-rich repeat containing) family is found in plants and animals, and serves as crucial regulators of inflammatory and innate immune response, though its functions are likely to extend greatly beyond innate immunity, and even beyond the immune system. This review discusses recent findings regarding the function of NLR proteins in the control of IL-1, NF-kappaB, and host response to pathogens including distinct forms of cell death. The review also covers recent advances regarding the biochemical nature of NLRs, its regulation by intracellular nucleotides and extracellular ATP, by the chaperone protein HSP90, and the ubiquitin ligase-associated protein SGT1. Its role in inflammation is linked to the formation of biochemical complexes such as the inflammasome, and its roles in cell death might be linked to the proposed formation of pyroptosome and necrosome.

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    • "Structural domains of the NLRs includes an N-terminal effector domain, a central nucleotide-binding domain (NBD or NACHT) and a C-terminal domain composed of a series of leucine-rich repeats (LRRs) (Ye & Ting, 2008). The N-terminal effector domain is used to subclassify the NLR proteins. "
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    ABSTRACT: The extensively studied cytokine IL-1β is an important mediator of the inflammatory response. However, dysregulated release of IL-1β can be detrimental and is attributed to the progression and pathogenesis of multiple inflammatory diseases including, rhuematoid arthritis (RA), atherosclerosis, type 2 diabetes (T2D), Alzheimers disease and gout. IL-1β is encoded as a pro-protein. A multi-protein molecular scaffold termed the "Inflammasome" is responsible for the tightly controlled and coordinated processing of pro-IL-1β. The activation of several NLR (nucleotide-binding oligomerization domain (NOD)-like receptor) family members and PYHIN (pyrin and HIN domain) proteins can drive the formation of inflammasomes. However, the exact biochemical mechanisms governing their activation have been the subject of much research. Different inflammasomes have been demonstrated to respond to the same pathogen inducing a cooperative immune response accountable for the clearance of infection. Here, we review current knowledge surrounding the biochemical regulation of the NLRP1, NLRP3, NLRC4, AIM2 and IFI16 inflammasomes.
    Critical Reviews in Biochemistry and Molecular Biology 06/2012; 47(5):424-43. DOI:10.3109/10409238.2012.694844 · 5.81 Impact Factor
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    • "However, some pathogen-derived molecules, such as foreign DNA or RNA, may reach intracellular compartments of infected cells where they are recognized by and bound to NOD-like receptors (NLRs) (Akira et al., 2006; Ye & Ting, 2008). The NLRs belong to a large family of cytosolic pattern recognition receptors (34 members in mice, 23 in human) (Jin & Flawell, 2010) that are able to recognize various pathogen associated molecular patterns or danger-associated molecular patterns and thereby initiate the innate immune response against invading pathogens and cellular signals of damage or stress. "
    Acute Phase Proteins - Regulation and Functions of Acute Phase Proteins, 10/2011; , ISBN: 978-953-307-252-4
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    • "Most recently, recognition of Ad by the NLRP3 inflammasome was shown to mediate the release of IL-1β (Muruve et al., 2008). NLRP3 contains an N-terminal pyrin domain, a central NACHT domain, NACHT-associated domain and 7 C-terminal leucine rich repeats (Ye and Ting, 2008). Numerous stimuli can activate the NLRP3 inflammasome by induction of reactive oxygen species or release of lysosomal cathepsins into the cytoplasm (Hornung and Latz; Schroder, Zhou, and Tschopp, 2010; Tschopp and Schroder). "
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    ABSTRACT: Adenovirus (Ad) endosomal membrane penetration activates the NLRP3 inflammasome by releasing lysosomal cathepsin B (catB) into the cytoplasm. We therefore examined the extent to which inflammasome activation correlates with Ad colocalization with catB-enriched lysosomes. Inflammasome activation, is greater during infections with Ad5 possessing an Ad16 fiber (Ad5F16gfp), or Ad5gfp neutralized by human serum, than Ad5gfp alone. Enhanced IL-1β release by Ad5F16gfp is partially due to increased TLR9 signaling but also correlates with greater release of catB into the cytoplasm. This increased TLR9 signaling and catB release correlates with a greater localization of Ad5F16gfp to lysosomes prior to endosomal escape. Another nonenveloped virus, reovirus, requires catB to penetrate cell membranes. However, reovirus did not release catB into the cytoplasm despite significantly greater colocalization with lysosomes compared to Ad5gfp and efficient membrane penetration. Thus, not only lysosomal localization, but the mechanism of membrane penetration influences viral activation of the NLRP3 inflammasome.
    Virology 02/2011; 412(2):306-14. DOI:10.1016/j.virol.2011.01.019 · 3.28 Impact Factor
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