Widera Darius, Martínez Aguilar Rocío, Cottrell Graeme S
Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights campus, Reading, UK.
Stem Cell Biology and Regenerative Medicine Group, School of Pharmacy, University of Reading, Whiteknights campus, Reading, UK; Unidad de Inmunología, IBIMER, Universidad de Granada, Granada, Spain.
Neural Regen Res. 2019 Jul;14(7):1196-1201. doi: 10.4103/1673-5374.251290.
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.
Toll样受体4（TLR4）和蛋白酶激活受体2（PAR2）在哺乳动物先天性免疫反应中起关键作用。值得注意的是，除了参与检测入侵病原体外，PAR2和TLR4还通过激活促炎或抗炎下游信号级联反应来调节细胞死亡诱导的无菌性炎症水平。在中枢神经系统中，越来越多的证据表明这两种受体都参与突触传递和大脑可塑性。此外，由于PAR2和TLR4在介导神经炎症中起重要作用，它们与神经退行性疾病的发生和发展相关，包括但不限于阿尔茨海默病、帕金森病和多发性硬化症。在本文中，我们总结了目前关于PAR2和TLR4之间合作的知识，讨论了潜在的相互作用水平，并强调了交叉偶联对神经炎症的影响。
