Kinoshita A, Kinoshita M, Akiyama H, Tomimoto H, Akiguchi I, Kumar S, Noda M, Kimura J
Department of Neurology, Kyoto University Graduate School of Medicine, Japan.
Am J Pathol. 1998 Nov;153(5):1551-60. doi: 10.1016/S0002-9440(10)65743-4.
Septins are evolutionarily conserved cytoskeletal GTPases that can form heteropolymer complexes involved in cytokinesis and other cellular processes. We detected expression of the human septin genes Nedd5, H5, Diff6, and hCDC100 in postmortem brain tissues using the reverse transcription-coupled polymerase chain reaction and their products by immunoblot analysis. Four antibodies directed against three septins, Nedd5, H5, and Diff6, consistently labeled neurofibrillary tangles, neuropil threads, and dystrophic neurites in the senile plaques in brains affected by Alzheimer's disease but did not label obvious structures in young control brains. Immunoelectron microscopy revealed that Nedd5 localized to the paired helical filaments. Pre-tangles, the precursory granular deposits that accumulate in the neuronal cytoplasm, also were labeled with the antibodies. These findings suggest that at least the three septins are associated with tau-based paired helical filament core, and may contribute to the formation of neurofibrillary tangle as integral constituents of paired helical filaments.
Septin蛋白是一类在进化上保守的细胞骨架GTP酶，可形成参与胞质分裂和其他细胞过程的异源聚合物复合物。我们通过逆转录聚合酶链反应检测了死后脑组织中人类Septin基因Nedd5、H5、Diff6和hCDC100的表达，并通过免疫印迹分析检测了它们的产物。四种针对三种Septin蛋白（Nedd5、H5和Diff6）的抗体一致标记了受阿尔茨海默病影响的大脑中淀粉样斑块中的神经原纤维缠结、神经毡丝和营养不良性神经突，但未标记年轻对照大脑中的明显结构。免疫电子显微镜显示Nedd5定位于双螺旋丝。在神经元细胞质中积累的前缠结（即前驱颗粒沉积物）也被这些抗体标记。这些发现表明，至少这三种Septin蛋白与基于tau的双螺旋丝核心相关，并可能作为双螺旋丝的组成部分，参与神经原纤维缠结的形成。
