Amyotrophic lateral sclerosis-linked mutant VAPB enhances TDP-43-induced motor neuronal toxicity
Amyotrophic lateral sclerosis-linked mutant VAPB enhances TDP-43-induced motor neuronal toxicity
复制标题
肌萎缩侧索硬化症相关突变体 VAPB 增强 TDP-43 诱导的运动神经元毒性
DOI：
10.1111/j.1471-4159.2011.07491.x
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发表时间：
2011
影响因子：
4.7
通讯作者：
Hiroaki Suzuki
中科院分区：
文献类型：
--
作者：
青山幾子、弓指孝博;他;Hiroaki Suzuki
J. Neurochem.(2011)119, 1099–1107.AbstractTransactive response DNA‐binding protein‐43 (TDP‐43) has been thought to be generally involved in the pathogenesis of most amyotrophic lateral sclerosis (ALS) patients although it remains undefined how TDP‐43 is involved in the ALS pathogenesis. In this study, we found that a P56S mutant of vesicle‐associated membrane protein‐associated protein B (VAPB), which has been identified to be a familial ALS‐causative protein, potentiated the TDP‐43‐induced motor neuronal cell death, while wild‐type VAPB conversely inhibited it. The P56S‐VAPB‐induced potentiation of the TDP‐43‐induced death was mediated by the up‐regulation of Bim expression at the mRNA level and other undefined mechanisms that leads to the enhancement of Bim and Bax activity. These observations suggest that TDP‐43 and P56S‐VAPB may co‐operate to involve the pathogenesis of ALS.
