MyD88 as a therapeutic target for inflammatory lung diseases

2018 
ABSTRACTIntroduction: Myeloid differentiation primary response protein 88 (MyD88) is a critical adaptor protein involved in Toll-like and IL-1 receptor family signaling controlling innate immune responses and inflammation. Genetic deletion of MyD88 function results in profound suppression of inflammation and reduced resistance of the host to pathogens indicating non-redundant roles of MyD88. The TIR domain is critical for MyD88 dimerization and signaling for TLR and IL-1R family receptor.Areas covered: Emerging evidence suggests that chemical disruption of the TIR domain attenuates cell activation and inhibits in vivo MyD88-dependent inflammation. We review the development of MyD88 dimerization disruptors as a novel therapeutic approach of respiratory diseases with a focus on COPD.Expert opinion: There is a proof of concept that therapeutic targeting of MyD88 is feasible and first preclinical data are highly promising. This opens a great opportunity to treat exacerbations of COPD and other chronic respira...
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