Toll-like receptor 4 and protease-activated receptor 2 in physiology and pathophysiology of the nervous system: more than just receptor cooperation?

Neural Regeneration Research
Darius WideraGraeme S Cottrell

Abstract

Toll-like receptor 4 (TLR4) and protease-activated receptor 2 (PAR2) play pivotal roles in the mammalian innate immune response. Notably, in addition to their involvement in detection of invading pathogens, PAR2 and TLR4 modulate the levels of cell death-induced sterile inflammation by activating pro- or anti-inflammatory downstream signaling cascades. Within the central nervous system, there is emerging evidence that both receptors are involved in synaptic transmission and brain plasticity. Furthermore, due to their prominent role in mediating neuroinflammation, PAR2 and TLR4 are associated with development and progression of neurodegenerative disorders including but not limited to Alzheimer's disease, Parkinson's disease and multiple sclerosis. In this article, we summarise the current knowledge on the cooperation between PAR2 and TLR4, discuss the potential cross-talk levels and highlight the impact of the cross-coupling on neuroinflammation.

References

Jan 1, 1994·The Journal of Experimental Medicine·E HailmanS D Wright
Sep 6, 1996·The Journal of Biological Chemistry·S K BöhmN W Bunnett
May 22, 2001·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·L ChiK N Dileepan
Jan 24, 2003·American Journal of Physiology. Cell Physiology·Dirk RoostermanNigel W Bunnett
Oct 1, 2003·The Journal of Experimental Medicine·Katherine A FitzgeraldDouglas T Golenbock
Mar 27, 2004·Physiological Reviews·Valeria S Ossovskaya, Nigel W Bunnett
Sep 24, 2004·Immunology·Eva M Pålsson-McDermott, Luke A J O'Neill
Feb 12, 2005·American Journal of Respiratory Cell and Molecular Biology·Sophie DulonMichel Chignard
Feb 15, 2005·The Journal of Biological Chemistry·Claire JacobNigel W Bunnett
Jul 12, 2007·The Journal of Biological Chemistry·Wolfgang KnechtNigel W Bunnett
Oct 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amir Afkhami-GoliChristopher Power
Nov 22, 2007·Trends in Molecular Medicine·Taro Kawai, Shizuo Akira
Dec 18, 2007·American Journal of Physiology. Lung Cellular and Molecular Physiology·Theo J MoraesGregory P Downey
Jul 16, 2008·The Journal of Biological Chemistry·Prasad RallabhandiStefanie N Vogel
May 18, 2011·The Journal of Biological Chemistry·Rithwik RamachandranMorley D Hollenberg
Jan 4, 2012·Nature Reviews. Drug Discovery·Rithwik RamachandranMorley D Hollenberg
Jun 12, 2012·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Leonid TarassishinSunhee C Lee
Jan 17, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jean-Philippe MichaudSerge Rivest
Mar 7, 2013·Scientific Reports·Carmen NoelkerAndreas Hartmann
May 3, 2013·PloS One·Carolyn R Casella, Thomas C Mitchell
Dec 21, 2013·British Journal of Pharmacology·M D HollenbergR Ramachandran
Feb 18, 2014·Journal of Neuroimmunology·Teresa TrottaMaria Antonietta Panaro
May 27, 2014·Frontiers in Endocrinology·Peishen ZhaoNigel W Bunnett
Aug 15, 2014·The Journal of Biological Chemistry·Peishen ZhaoNigel W Bunnett
Feb 28, 2016·Current Opinion in Cell Biology·Roberto VillaseñorMarino Zerial
Nov 5, 2016·Biochimica Et Biophysica Acta·Marie-Theres ZeunerDarius Widera
Aug 10, 2017·Mediators of Inflammation·Marie-Theres ZeunerDarius Widera

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Citations

May 29, 2020·Science Translational Medicine·Nurit P AzouzMarc E Rothenberg
Aug 9, 2020·Immunopharmacology and Immunotoxicology·Ramachandran Vidhya, Carani Venkatraman Anuradha
May 14, 2021·Frontiers in Immunology·Sílvia LlorensTomás Segura

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Methods Mentioned

BETA
nuclear translocation
nuclear
electrophoretic mobility shift assay
co-immunoprecipitation
proximity
fluorescence recovery after photobleaching

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