Mechanisms of NF-κB p65 and strategies for therapeutic manipulation.

摘要: The transcription factor NF-κB is a critical regulator of immune and inflammatory responses. In mammals, the NF-κB/Rel family comprises five members: p50, p52, p65 (Rel-A), c-Rel, Rel-B proteins, which form homo- or heterodimers remain as an inactive complex with inhibitory molecules called IκB proteins in resting cells. Two distinct signaling pathways have been described: 1) canonical pathway primarily activated by pathogens mediators, 2) noncanonical mostly developmental cues. most abundant pathologic stimuli via p65:p50 heterodimer. Disproportionate increase subsequent transactivation effector integral to pathogenesis many chronic diseases such rheumatoid arthritis, bowel disease, multiple sclerosis, even neurodegenerative pathologies. Hence, has pivotal point for intense drug discovery development. This review begins overview p65-mediated followed discussion strategies that directly target context inflammation.