Diseño de péptidos inhibidores de interacciones de la subunidad GluN2B del receptor NMDA en isquemia
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El receptor NMDA constituye el principal subtipo de receptores de glutamato implicados en procesos fisiológicos tales como desarrollo neuronal, plasticidad sináptica, memoria y aprendizaje y numerosas condiciones patológicas como daño isquémico, dolor crónico, psicosis, y otros trastornos degenerativos. Se ha sugerido la regulación por fosforilación como un mecanismo de alteración de la permeabilidad relativa del NMDAR a Ca2+ durante la isquemia. En este trabajo se diseñó una serie de péptidos basados en interacciones de la subunidad GluN2B con las proteínas DAPK1, SRC y D2R, relacionadas con los efectos generados tras un evento isquémico. La identificación de sitios de unión entre estas moléculas y GluN2B permitió hacer un diseño in silico de péptidos que eventualmente pueden bloquear dichas interacciones y reducir los efectos nocivos de patologías como la isquemia. Nuestros resultados demuestran que el diseño racional de péptidos es una buena estrategia para la generación de nuevos agentes terapéuticos.
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