Reduced expression of BTBD10, an Akt activator, leads to motor neuron death
Reduced expression of BTBD10, an Akt activator, leads to motor neuron death
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DOI：
10.1038/cdd.2012.19
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发表时间：
2012-08-01
影响因子：
12.4
通讯作者：
Matsuoka, M.
中科院分区：
文献类型：
--
作者：
Nawa, M.;Kage-Nakadai, E.;Matsuoka, M.
BTBD10是Akt的相互作用因子，通过降低蛋白磷酸酶2a介导的Akt的去磷酸化和失活来激活Akt。BTBD10的过表达可抑制家族性肌萎缩性侧索硬化症（ALS）相关超氧化物歧化酶1 （SOD1）突变体G93A-SOD1诱导的运动神经元死亡。在本研究中，我们进一步研究了btbd10介导的运动神经元死亡的抑制。我们发现小干扰rna介导的BTBD10表达抑制导致培养的运动神经元死亡。在秀丽隐杆线虫（C. elegans）中，bbbd -10基因的破坏不仅会导致神经元（包括运动神经元和触摸受体神经元）的丢失，还会导致运动缺陷。此外，我们发现散发性ALS患者和过表达G93A-SOD1的转基因小鼠（G93A-SOD1转基因小鼠）的运动神经元中BTBD10的表达普遍降低。总之，这些结果表明，BTBD10的表达降低导致运动神经元在体内和体外的死亡。细胞死亡与分化（2012）19,1398-1407；doi: 10.1038 / cdd.2012.19;2012年3月2日在线发布
BTBD10, an Akt interactor, activates Akt by decreasing the protein phosphatase 2A-mediated dephosphorylation and inactivation of Akt. Overexpression of BTBD10 suppresses motor neuron death that is induced by a familial amyotrophic lateral sclerosis (ALS)-linked superoxide dismutase 1 (SOD1) mutant, G93A-SOD1 in vitro. In this study, we further investigated the BTBD10-mediated suppression of motor neuron death. We found that the small interfering RNA-mediated inhibition of BTBD10 expression led to the death of cultured motor neurons. In Caenorhabditis elegans (C. elegans), disruption of the btbd-10 gene caused not only loss of neurons, including both motor and touch-receptor neurons, but also a locomotion defect. In addition, we found that the expression of BTBD10 was generally decreased in the motor neurons from patients of sporadic ALS and transgenic mice overexpressing G93A-SOD1 (G93A-SOD1-transgenic mice). Collectively, these results suggest that the reduced expression of BTBD10 leads to motor neuron death both in vitro and in vivo. Cell Death and Differentiation (2012) 19, 1398-1407; doi:10.1038/cdd.2012.19; published online 2 March 2012