NF κB and Kidney Injury

Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co-inhibitor of the JNK-activating kinase MKK7, and the NFκB-regulated antiapoptotic factor GADD45β could be of clinical value through GADD45B expression in multiple myeloma, which was confirmed to be effective in a subsequent clinical trial (146). However, considering the complexity of the NFκB pathways and the crosstalk between the pathways, there are numerous NFκB-independent side effects that are unrelated to the on-target effects of the inhibitors (147). Therefore, a more specific regulation of NFκB in the targeted disease must be cell-specific. In addition, as the NFκB system has a broad impact on all kinds of tissues, modulation of NFκB in diseased cells without effecting normal cells must be guaranteed. Therefore, we also need to focus on an appropriate delivery system that will transfer small-molecular inhibitors or gen...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research

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