Truncated wild-type SOD1 and FALS-linked mutant SOD1 cause neural cell death in the chick embryo spinal cord
Truncated wild-type SOD1 and FALS-linked mutant SOD1 cause neural cell death in the chick embryo spinal cord
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DOI：
10.1016/j.nbd.2005.07.006
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发表时间：
2006-01-01
影响因子：
6.1
通讯作者：
Roos, RP
中科院分区：
文献类型：
--
作者：
Ghadge, GD;Wang, LJ;Roos, RP
大约10%的肌萎缩侧索硬化症(ALS)病例是家族性的(FALS)，与25%的FALS病例类似，是由超氧化物歧化酶-1(SOD1)突变引起的。突变(MT)SOD1由于突变蛋白的毒性而杀死运动神经元；然而，毒性的基础尚不清楚。我们将野生型(WT)、截短型WT或MTSOD1表达载体电穿孔到鸡胚胎脊髓。MTSOD1和截短WTSOD1(最小36个氨基酸残基)聚集在细胞质中，导致细胞死亡。这些结果提示，MTSOD1和截短WTSOD1由于错误折叠导致神经细胞死亡，SOD1多肽可能是MTSOD蛋白水解性消化的结果，在FALS的发病机制中发挥了作用。鸡胚胎脊髓电穿孔是研究神经退行性疾病的有用系统，因为它提供了有效的基因输送到活体内原位的神经细胞。(C)2005 Elsevier Inc.保留所有权利。
Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (FALS), and similar to 25% of FALS cases are caused by mutations in superoxide dismutase-1 (SOD1). Mutant (MT) SOD1 kills motor neurons because of the mutant protein's toxicity; however, the basis for toxicity is unknown. We electroporated wild-type (WT), truncated WT or MTSOD1 expression constructs into the chick embryo spinal cord. MTSOD1 and truncated WTSOD1 (as small as 36 amino acid residues in length) aggregated in the cytoplasm of cells and caused cell death. These results suggest that MTSOD1 and truncated WTSOD1 lead to neural cell death because of misfolding, and that SOD1 peptides, possibly as a result of proteolytic digestion of MTSOD, play a role in FALS pathogenesis. Electroporation of the chick embryo spinal cord is a useful system in which to investigate neurodegenerative diseases because it provides efficient delivery of genes into neural cells in situ within a living organism. (c) 2005 Elsevier Inc. All rights reserved.