Small-molecule antagonism of the interaction of the RAGE cytoplasmic domain with DIAPH1 reduces diabetic complications in mice.

ABSTRACT: The macro- and microvascular complications of type 1 and 2 diabetes lead to increased disease severity and mortality. The receptor for advanced glycation end products (RAGE) can bind AGEs and multiple proinflammatory ligands that accumulate in diabetic tissues. Preclinical studies indicate that RAGE antagonists have beneficial effects on numerous complications of diabetes. However, these antagonists target the extracellular domains of RAGE, which bind distinct RAGE ligands at diverse sites in the immunoglobulin-like variable domain and two constant domains. The cytoplasmic tail of RAGE (ctRAGE) binds to the formin, Diaphanous-1 (DIAPH1), and this interaction is important for RAGE signaling. To comprehensively capture the breadth of RAGE signaling, we developed small-molecule antagonists of

SUBMITTER: Manigrasso MB 

PROVIDER: S-EPMC8669775 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature