NF-kB control of neuronal apoptosis in Alzheimer disease

在2012财年，我们实现了以下目标： 1. 确定5种考克斯-2抑制剂中的3种抑制CD 4 + T细胞中的c-Rel活化。 所有抑制Rel的药物也阻止了我们先前确定为塞来昔布靶点的几种Rel反应性TNF和TNF-R超家族成员的上调。 2. 我们发现，塞来昔布在体外抑制向炎性TH 17细胞的分化。这不是由于抑制谱系决定转录因子ROR-T。 3. 使用不同剂量的塞来昔布，我们发现Rel的最大抑制与ER应激的激活一致。 早期研究表明内质网应激导致NF- B表达上调。 我们的观察结果提供了一个新的连接ER压力和下调一个特定的NF-B家族成员。 目前正在修订描述这些调查结果的手稿。

During FY12 we accomplished the following: 1. Determined that 3 out of 5 COX-2 inhibitors suppressed c-Rel activation in CD4+ T cells. All those that inhibited Rel also prevented up-regulation of several Rel-responsive TNF and TNF-R super family members that we previously identified as targets of celecoxib. 2. We found that celecoxib inhibited differentiation to inflammatory TH17 cells in vitro This was not due to suppression of the lineage-determining transcription factor RORϒ-T. 3. Using celecoxib at different doses we found that maximal suppression of Rel coincided with activation of ER stress. Earlier studies have indicated that ER stress leads to up-regulation of NF-κB. Our observations provide a novel connection between ER stress and down-regulation of a specific NF-κB family member. A manuscript describing these findings is currently under revision.