Sako Wataru, Ito Hidefumi, Yoshida Mari, Koizumi Hidetaka, Kamada Masaki, Fujita Koji, Hashizume Yoshio, Izumi Yuishin, Kaji Ryuji
Department of Clinical Neuroscience, The University of Tokushima Graduate School, Tokushima, Japan.
Clin Neuropathol. 2012 Nov-Dec;31(6):418-23. doi: 10.5414/NP300493.
Nuclear factor κ B (NF-κB) is involved in the pathogenesis of a number of neurodegenerative disorders with neuroinflammation. In order to clarify the role of NF-κB in ALS, immunohistochemical studies with an antibody that recognizes the p65 subunit of NF-κB were performed on the spinal anterior horn of 4 patients with sporadic ALS (sALS), 1 patient with optineurin-mutated ALS (OPTN-ALS), and 3 normal controls (NC). In patients with sALS or OPTN-ALS, the expression pattern of NF-κB was altered when compared to that of NC; NF-κB immunoreactivity tended to be absent from neuronal nucleus and was increased in microglia. The down-regulation of NF-κB in neuronal nucleus might contribute to a loss of neuroprotection, or neurons with nuclear NF-κB might be lost immediately after its activation. The microglial induction of NF-κB might contribute to neuroinflammation. In conclusion, NF-κB signaling pathway could have a key role in the pathomechanism of ALS.
核因子κB（NF-κB）参与了许多伴有神经炎症的神经退行性疾病的发病机制。为了阐明NF-κB在肌萎缩侧索硬化症（ALS）中的作用，我们使用一种识别NF-κB p65亚基的抗体，对4例散发性ALS（sALS）患者、1例视紫质突变型ALS（OPTN-ALS）患者的脊髓前角以及3名正常对照（NC）进行了免疫组织化学研究。在sALS或OPTN-ALS患者中，与NC相比，NF-κB的表达模式发生了改变；NF-κB免疫反应性在神经元细胞核中往往缺失，而在小胶质细胞中增加。神经元细胞核中NF-κB的下调可能导致神经保护作用丧失，或者细胞核中含有NF-κB的神经元在激活后可能立即丢失。小胶质细胞对NF-κB的诱导可能导致神经炎症。总之，NF-κB信号通路可能在ALS的发病机制中起关键作用。
