NLRC5: A Potential Target for Central Nervous System Disorders

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Jul 5

PMID 34220868

Citations 7

Authors

Lu Zhang

Cui Jiao

Lingjuan Liu

Aiping Wang

Li Tang

Yi Ren

Peng Huang

Jie Xu

Dingan Mao

Liqun Liu

Affiliations

Soon will be listed here.

Abstract

Nucleotide oligomerization domain-like receptors (NLRs), a class of pattern recognition receptors, participate in the host's first line of defense against invading pathogenic microorganisms. NLR family caspase recruitment domain containing 5 (NLRC5) is the largest member of the NLR family and has been shown to play an important role in inflammatory processes, angiogenesis, immunity, and apoptosis by regulating the nuclear factor-κB, type I interferon, and inflammasome signaling pathways, as well as the expression of major histocompatibility complex I genes. Recent studies have found that NLRC5 is also associated with neuronal development and central nervous system (CNS) diseases, such as CNS infection, cerebral ischemia/reperfusion injury, glioma, multiple sclerosis, and epilepsy. This review summarizes the research progress in the structure, expression, and biological characteristics of NLRC5 and its relationship with the CNS.

Citing Articles

17β-estradiol promotes the progression of temporomandibular joint osteoarthritis by regulating the FTO/IGF2BP1/m6A-NLRC5 axis.

Xue X, Li C, Chen S, Zheng Y, Zhang F, Xu Y Immun Inflamm Dis. 2024; 12(8):e1361.

PMID: 39092772 PMC: 11295093. DOI: 10.1002/iid3.1361.

A tale of endurance: bats, viruses and immune dynamics.

Apoorva , Singh S Future Microbiol. 2024; 19(9):841-856.

PMID: 38648093 PMC: 11382704. DOI: 10.2217/fmb-2023-0233.

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.

Lundin J, Peters U, Hu Y, Ammous F, Avery C, Benjamin E Epigenetics. 2024; 19(1):2333668.

PMID: 38571307 PMC: 10996836. DOI: 10.1080/15592294.2024.2333668.

Adaptor molecules mediate negative regulation of macrophage inflammatory pathways: a closer look.

Baig M, Barmpoutsi S, Bharti S, Weigert A, Hirani N, Atre R Front Immunol. 2024; 15:1355012.

PMID: 38482001 PMC: 10933033. DOI: 10.3389/fimmu.2024.1355012.

Harnessing deep learning into hidden mutations of neurological disorders for therapeutic challenges.

Yang S, Kim S, Kang M, Joo J Arch Pharm Res. 2023; 46(6):535-549.

PMID: 37261600 DOI: 10.1007/s12272-023-01450-5.

References

Labbe K, Saleh M . Cell death in the host response to infection. Cell Death Differ. 2008; 15(9):1339-49. DOI: 10.1038/cdd.2008.91. View

Zong Z, Song Y, Xue Y, Ruan X, Liu X, Yang C . Knockdown of LncRNA SCAMP1 suppressed malignant biological behaviours of glioma cells via modulating miR-499a-5p/LMX1A/NLRC5 pathway. J Cell Mol Med. 2019; 23(8):5048-5062. PMC: 6653555. DOI: 10.1111/jcmm.14362. View

Robbins G, Truax A, Davis B, Zhang L, Brickey W, Ting J . Regulation of class I major histocompatibility complex (MHC) by nucleotide-binding domain, leucine-rich repeat-containing (NLR) proteins. J Biol Chem. 2012; 287(29):24294-303. PMC: 3397855. DOI: 10.1074/jbc.M112.364604. View

Hu Z, Chai J . Structural Mechanisms in NLR Inflammasome Assembly and Signaling. Curr Top Microbiol Immunol. 2016; 397:23-42. DOI: 10.1007/978-3-319-41171-2_2. View

Meeks K, Henneman P, Venema A, Burr T, Galbete C, Danquah I . An epigenome-wide association study in whole blood of measures of adiposity among Ghanaians: the RODAM study. Clin Epigenetics. 2017; 9:103. PMC: 5609006. DOI: 10.1186/s13148-017-0403-x. View

Benko S, Magalhaes J, Philpott D, Girardin S . NLRC5 limits the activation of inflammatory pathways. J Immunol. 2010; 185(3):1681-91. DOI: 10.4049/jimmunol.0903900. View

Shi Y, Zhang Y, Liu B, Li C, Wu J, Li Y . Nomilin protects against cerebral ischemia-reperfusion induced neurological deficits and blood-brain barrier disruption via the Nrf2 pathway. Food Funct. 2019; 10(9):5323-5332. DOI: 10.1039/c9fo01481k. View

Tong Y, Cui J, Li Q, Zou J, Wang H, Wang R . Enhanced TLR-induced NF-κB signaling and type I interferon responses in NLRC5 deficient mice. Cell Res. 2012; 22(5):822-35. PMC: 3343662. DOI: 10.1038/cr.2012.53. View

Saylor D, Dickens A, Sacktor N, Haughey N, Slusher B, Pletnikov M . HIV-associated neurocognitive disorder--pathogenesis and prospects for treatment. Nat Rev Neurol. 2016; 12(4):234-48. PMC: 4937456. DOI: 10.1038/nrneurol.2016.27. View

10.

Kumar M, Belcaid M, Nerurkar V . Identification of host genes leading to West Nile virus encephalitis in mice brain using RNA-seq analysis. Sci Rep. 2016; 6:26350. PMC: 4876452. DOI: 10.1038/srep26350. View

11.

Tang F, Xu Y, Zhao B . NLRC5: new cancer buster?. Mol Biol Rep. 2020; 47(3):2265-2277. DOI: 10.1007/s11033-020-05253-5. View

12.

Gharagozloo M, Gris K, Mahvelati T, Amrani A, Lukens J, Gris D . NLR-Dependent Regulation of Inflammation in Multiple Sclerosis. Front Immunol. 2018; 8:2012. PMC: 5778124. DOI: 10.3389/fimmu.2017.02012. View

13.

Cao L, Wu X, Hu Y, Xue N, Nie P, Chang M . The discrepancy function of NLRC5 isoforms in antiviral and antibacterial immune responses. Dev Comp Immunol. 2018; 84:153-163. DOI: 10.1016/j.dci.2018.02.013. View

14.

Zhu C, Zou C, Guan G, Guo Q, Yan Z, Liu T . Development and validation of an interferon signature predicting prognosis and treatment response for glioblastoma. Oncoimmunology. 2019; 8(9):e1621677. PMC: 6685507. DOI: 10.1080/2162402X.2019.1621677. View

15.

Jongsma M, Guarda G, Spaapen R . The regulatory network behind MHC class I expression. Mol Immunol. 2017; 113:16-21. DOI: 10.1016/j.molimm.2017.12.005. View

16.

Lenart N, Brough D, Denes A . Inflammasomes link vascular disease with neuroinflammation and brain disorders. J Cereb Blood Flow Metab. 2016; 36(10):1668-1685. PMC: 5076791. DOI: 10.1177/0271678X16662043. View

17.

Gutte P, Jurt S, Grutter M, Zerbe O . Unusual structural features revealed by the solution NMR structure of the NLRC5 caspase recruitment domain. Biochemistry. 2014; 53(19):3106-17. DOI: 10.1021/bi500177x. View

18.

Bergen S, ODushlaine C, Ripke S, Lee P, Ruderfer D, Akterin S . Genome-wide association study in a Swedish population yields support for greater CNV and MHC involvement in schizophrenia compared with bipolar disorder. Mol Psychiatry. 2012; 17(9):880-6. PMC: 3724337. DOI: 10.1038/mp.2012.73. View

19.

Falcao A, van Bruggen D, Marques S, Meijer M, Jakel S, Agirre E . Disease-specific oligodendrocyte lineage cells arise in multiple sclerosis. Nat Med. 2018; 24(12):1837-1844. PMC: 6544508. DOI: 10.1038/s41591-018-0236-y. View

20.

Nagyoszi P, Nyul-Toth A, Fazakas C, Wilhelm I, Kozma M, Molnar J . Regulation of NOD-like receptors and inflammasome activation in cerebral endothelial cells. J Neurochem. 2015; 135(3):551-64. DOI: 10.1111/jnc.13197. View