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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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    • "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. "
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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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