Department of Biology, Dartmouth College, Hanover, NH 03755, USA.
Proc Natl Acad Sci U S A. 2012 Mar 6;109(10):E605-12. doi: 10.1073/pnas.1110666109. Epub 2012 Feb 10.
Photoreceptor cell death accompanying many retinal degenerative disorders results in irreversible loss of vision in humans. However, the precise molecular pathway that executes cell death is not known. Our results from a Drosophila model of retinal degeneration corroborate previously reported findings that the developmental apoptotic pathway is not involved in photoreceptor cell demise. By undertaking a candidate gene approach, we find that players involved in the immune response against gram-negative bacteria are involved in retinal degeneration. Here, we report that the NF-κB transcription factor Relish regulates neuronal cell death. Retinal degeneration is prevented in genetic backgrounds that block Relish activation. We also report that the N-terminal domain of Relish encodes unique toxic functions. These data uncover a unique molecular pathway of retinal degeneration in Drosophila and identify a previously unknown function of NF-κB signaling in cell death.
许多视网膜退行性疾病伴随着光感受器细胞死亡，导致人类视力不可逆转地丧失。然而，执行细胞死亡的确切分子途径尚不清楚。我们在果蝇视网膜变性模型中的研究结果证实了先前的研究结果，即发育性细胞凋亡途径不参与光感受器细胞的死亡。通过进行候选基因方法，我们发现参与针对革兰氏阴性菌的免疫反应的参与者参与了视网膜变性。在这里，我们报告 NF-κB 转录因子 Relish 调节神经元细胞死亡。在阻止 Relish 激活的遗传背景下，视网膜变性得以预防。我们还报告说，Relish 的 N 端结构域编码独特的毒性功能。这些数据揭示了果蝇中独特的视网膜变性分子途径，并确定了 NF-κB 信号在细胞死亡中的以前未知的功能。
