Myeloid differentiation primary response 88 (MyD88) (MyD88)

Myeloid differentiation primary response 88 (MyD88) is a fundamental adapter protein that bridges the detection of pathogens to the initiation of the innate immune response [UniProt P26358]. It serves as a critical signaling hub for nearly all Toll-like receptors (TLRs), with the exception of TLR3, and members of the interleukin-1 receptor (IL-1R) family [NIH/NCBI Gene ID: 4615]. Upon receptor activation, MyD88 undergoes oligomerization to form the myddosome complex, which recruits and activates interleukin-1 receptor-associated kinases (IRAKs), ultimately triggering the NF-kappaB and MAPK signaling pathways [Lin et al., 2010, Nature]. In the context of disease, the gain-of-function L265P mutation in the MYD88 gene is a defining driver in Waldenström macroglobulinemia and various B-cell lymphomas, where it promotes constitutive pro-survival signaling [Treon et al., 2012, NEJM]. Pharmacological targeting of MyD88 focuses on small molecules that disrupt its TIR domain interactions or dimerization, offering potential therapeutic avenues for both hematologic malignancies and chronic inflammatory disorders [Olson et al., 2015, Scientific Reports]. However, therapeutic inhibition must be carefully managed, as genetic MyD88 deficiency in humans is associated with life-threatening susceptibility to invasive pyogenic bacterial infections [von Bernuth et al., 2008, Science].

Other names

Myeloid differentiation primary response protein MyD88MYD88D

Inhibition of MyD88 homodimerization or disruption of the Toll/interleukin-1 receptor (TIR) domain-mediated recruitment to upstream receptors.