Figure 6. Schematic representation of potential effects of VELCADE on TLR signaling pathway.
Stroke induces the activation of vascular TLR signal, which leads to upregulation of proinflammatory genes via the activation of NF-κB. VELCADE inactivates NF-kB through either directly blocking stroke-activated TLR2 and TLR4 or indirectly repressing IRAK1 by VELCADE upregulated miR-146a, which consequently downregulates proinflammatory gene expression. Thus, VELCADE acts on a multi-level inhibition of TLR signaling in ischemic cerebral vessels.