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Fig. 5 | Journal of Neuroinflammation

Fig. 5

From: Novel TNF receptor-1 inhibitors identified as potential therapeutic candidates for traumatic brain injury

Fig. 5

TNF-R1 inhibitors identified as potential therapeutic candidates for diffuse traumatic brain injury. a TNF binds the extracellular domain of TNF-R1 which leads to TNF-induced activation of NF-κB following the phosphorylation ubiquitination and degradation of inhibitor of κB (IκB) proteins, thus retaining NF-κB within the cytoplasm. NF-κB activation signals inflammatory pathways leading to an increase in cytokines and sleep, and a decrease in functional outcome. b Experimental cavity-induced allosteric modifiers (CIAMs) of TNF-R1 bind to the receptor and prevent TNF from binding. This prevents TNF-induced activation of NF-κB which dampens downstream inflammatory signaling reducing cytokine production, preventing inflammation-induced sleep, and improving functional outcome

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