Role of Adaptor Protein Myeloid Differentiation 88 (MyD88) in Post-Subarachnoid Hemorrhage Inflammation: A Systematic Review

Abstract

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.

Achyranthes bidentata Polysaccharide Activates Nuclear Factor-Kappa B and Promotes Cytokine Production in J774A.1 Cells Through TLR4/MyD88 Signaling Pathway

“…Upon ligand binding to TLR4, the adaptor protein, primarily MyD88, is recruited. MyD88 is further associated with IL-1R-associated kinase (IRAK) family kinases and results in the formation of a "myddosome" complex, which initiates various responses, and triggering the downstream pathway (Ahmed et al, 2021;Saikh, 2021). Our results showed that ABPS can significantly increase the mRNA and protein expression of MyD88.…”

“…The TLR intracellular signals ultimately lead to the activation and nuclear translocation of the transcription factors such as NF-κB and IRFs (El-Zayat et al, 2019), which dictate the consequences of the innate immune response activation (Ahmed et al, 2021). The nuclear translocation of NF-κB regulates the expression of a variety of genes, associated with the innate and adaptive immune responses (Hayden and Ghosh, 2011).…”

“…It has been known that polysaccharides can directly or indirectly activate macrophages, natural killer cells, T lymphocytes, dendritic cells, etc., increase the secretion of cytokines, improve the antibody level, and enhance the immune response through different mechanisms (Yu et al, 2018;Chen et al, 2019;Li Y. et al, 2021). The innate immune response relies on several germ line-encoded pattern-recognition receptors (PRRs) (Ahmed et al, 2021). Toll-like receptors (TLRs), as one of the largest and well-characterized PRRs, have a key role in the immune response (El-Zayat et al, 2019;Mokhtari et al, 2021).…”

Inflammation and Anti-Inflammatory Targets after Aneurysmal Subarachnoid Hemorrhage

“…DAMPs are initiators of the immune response; therefore, approaches that can antagonize or scavenge the released DAMPs, e.g., HMGB1, have been described to ameliorate the inflammation [ 11 , 15 ]. Several pattern recognition receptors and their downstream signaling pathways represent the next targets in mediating inflammation [ 25 ]. Toll-like receptors (TLRs) are among the well-established PRRs known to upregulate inflammation [ 26 ].…”

Role of Toll-Like Receptors in Neuroimmune Diseases: Therapeutic Targets and Problems

“…To date, 13 active members of the TLRs family have been identified in mammals, including 10 in humans (TLR1-10) and 12 in mice (TLR1-9 and TLR11-13) ( 26 ). TLRs are largely categorized into two subfamilies based on their localization, such as transmembrane and intracellular regions ( 21 ).…”