RESUMEN

Toll-like receptors are an integral part of innate immunity in the central nervous system (CNS); they orchestrate a robust defense in response to both exogenous and endogenous danger signals. Recently, toll-like receptor 4 (TLR4) has emerged as a therapeutic target for the treatment of CNS-related diseases such as sepsis and chronic pain. We herein report a chemical biology approach by using a rationally designed peptide inhibitor to disrupt the TLR4-MD2 association, thereby blocking TLR4 signaling.

Asunto(s)

Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Péptidos/farmacología , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/metabolismo , Proteínas Adaptadoras Transductoras de Señales/química , Animales , Línea Celular , Biología Computacional , Antígeno 96 de los Linfocitos , Ratones , Modelos Moleculares , Péptidos/síntesis química , Unión Proteica/efectos de los fármacos , Conformación Proteica , Receptor Toll-Like 4/química