Department of Basic Medical Sciences, Imran Idrees College of Pharmacy, University of the Punjab, Sialkot 51310, Pakistan.
Department of Pharmacology, Faculty of Pharmacy, University of Central Punjab (UCP), Lahore 54000, Pakistan.
Int J Mol Sci. 2021 Apr 18;22(8):4185. doi: 10.3390/ijms22084185.
Myeloid differentiation 88 (MyD88) is a well-established inflammatory adaptor protein. It is one of the essential downstream proteins of the toll-like receptor 4 (TLR4) signaling pathway. TLRs are pattern recognition receptors that are usually activated by the damage-associated molecular pattern molecules (DAMPs). Sterile inflammation is triggered by the endogenous DAMPs released in response to global cerebral ischemia and from extravasated blood after subarachnoid hemorrhage (SAH). In this review, we highlight the importance of the neuroinflammatory role of the MyD88 in the SAH. We also explore a few possible pharmacological agents that can be used to decrease SAH-associated neuroinflammation by modulating the MyD88 dependent functions. Pharmacological agents such as flavonoids, melatonin, fluoxetine, pentoxifylline and progesterone have been investigated experimentally to reduce the SAH-associated inflammation. Inhibition of the MyD88 not only reduces the expression of pro-inflammatory cytokines, but also potentially inhibits other processes that can augment the SAH associated inflammation. Further investigations are required to translate these findings in the clinical setting.
髓样分化因子 88（MyD88）是一种成熟的炎症衔接蛋白。它是 Toll 样受体 4（TLR4）信号通路的必需下游蛋白之一。TLRs 是模式识别受体，通常由损伤相关分子模式（DAMPs）激活。在全脑缺血和蛛网膜下腔出血（SAH）后漏出的血液中，内源性 DAMPs 的释放会引发无菌性炎症。在这篇综述中，我们强调了 MyD88 在 SAH 中的神经炎症作用的重要性。我们还探讨了几种可能的药理学制剂，通过调节 MyD88 依赖性功能来减少与 SAH 相关的神经炎症。黄酮类化合物、褪黑素、氟西汀、己酮可可碱和孕酮等药理学制剂已被实验研究用于减轻与 SAH 相关的炎症。抑制 MyD88 不仅可以降低促炎细胞因子的表达，还可以潜在地抑制其他可能增强与 SAH 相关的炎症的过程。需要进一步的研究将这些发现转化为临床应用。
