1. Dissecting a Hub for Immune Response: Modeling the Structure of MyD88
Chiara Naro, Claudio Sette 
Structure 
Volume 24, Issue 3, Pages (March 2016)
DOI: /j.str
Copyright © 2016 Elsevier Ltd Terms and Conditions

2. Figure 1
MYD88-Regulated Signaling Pathways and Their Relevance in Human Disease
(A) Schematic representation of the crucial role of MyD88 in the TLR/IL-1R signaling pathways. Once activated by their ligands, i.e., pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and interleukins, TLR/IL-1R recruit MyD88 through direct homophilic interaction between TIR domains or through the bridging adaptor MyD88 adaptor-like (MAL) protein. Oligomerization of MyD88 with IRAKs through their DDs leads then to the assembly of the Myddosome, a macromolecular complex that activates TRAF6 and TRAF3 and promotes the expression of pro-inflammatory cytokines and IFN-responsive genes through the activation of MAPKs, NF-kB, and IRFs transcription factors.
(B) Hyperactivation of MyD88 can be elicited by several causes, such as activating mutations in its gene, like the L265P reported in B cell malignancies, its deregulated expression, or persistence of chronic inflammation. Inhibition of MyD88 activity represents an attractive therapeutic approach for the treatment of different human diseases correlated with hyperactivation of TLR pathways (i.e., cancer, autoimmune and neurodegenerative diseases). Currently available approaches for inhibition of MYD88 activity are peptides and compounds that inhibit the TIR- and DD-mediated MYD88 interactions and anti-sense oligonucleotides (ASOs), forcing the expression of the shorter MYD88s splice variant, which is unable to interact with IRAKs.
Structure  , DOI: ( /j.str )
Copyright © 2016 Elsevier Ltd Terms and Conditions