Nuclear factor kappa B (NF-κB) family transcription factors are the master regulators. NF-κB is indispensable for a wide variety of biological processes including inflammation and the immune system. NF-kB functions as a dimer and is retained in the cytoplasm in an inactive form. When stimulated, NF-kB is released and undergoes active nuclear translocation, leading to the initiation of NF-κB dependent gene transcription for the activation of downstream processes.
Alpha-tubulin plays an important role in regulating microtubule stability and function. Meanwhile, the microtubule cytoskeleton also can modulate gene transcription through NF-κB signaling. The depolymerization of microtubules can activate NF-κB, resulting in the generation of inflammation.
SB26019 is a potent anti-neuroinflammatory agent.
SB26019 can induce monomeric α-tubulin formation. Then tubulin monomer recruits p65, inhibiting its translocation from the cytosol to the nucleus and blocking NF-κB-mediated inflammatory pathways. On the one hand, SB26019 can suppress the production of inflammatory marker genes, such as Ccl2, Cxcl10, Il-1β, Il-6, Nos2, and Tnf. SB26019 also induces IκB degradation in a time- and dose-dependent manner. Besides, SB26019-induced α-tubulin monomer inhibits p65 translocation in J774A.1 and RAW264.7 murine macrophage cells. On the other hand, SB26019 suppressed microglial activation by downregulating lba-1 and proinflammatory cytokines. Intraperitoneal administration of SB26019 also ameliorates neuroinflammation in vivo.
In conclusion, SB26019 has an anti-neuroinflammatory activity that regulates NF-κB activation by inducing monomeric α-tubulin formation.