Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1
Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1
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DOI：
10.1126/science.281.5384.1851
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发表时间：
1998-09-18
期刊：
影响因子：
56.9
通讯作者：
Cleveland, DW
中科院分区：
文献类型：
--
作者：
Bruijn, LI;Houseweart, MK;Cleveland, DW
对在酶超氧化物歧化酶（SOD 1）中表达常见的肌萎缩性侧索硬化症（ALS）相关突变的转基因小鼠的分析表明，运动神经元死亡是由一种或多种MUR介导的毒性特性引起的。在测试疾病机制时，发现野生型SOD1的消除和升高对mu介导的疾病没有影响，这表明使用SOD模拟物不太可能是有效的治疗，并提出了毒性是否来自超氧化物介导的氧化应激的问题。含有SOD 1的聚集体常见于由不同突变体引起的疾病，这意味着未鉴定的必需组分或组分的共聚集或错误折叠的突变体的异常催化是部分突变体介导的毒性的基础。
Analysis of transgenic mice expressing familiar amyotrophic Lateral sclerosis (ALS)-linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1 were found to have no effect on mutant-mediated disease, which demonstrates that the use of SOD mimetics is unlikely to be an effective therapy and raises the question of whether toxicity arises from superoxide-mediated oxidative stress. Aggregates containing SOD1 were common to disease caused by different mutants, implying that coaggregation of an unidentified essential component or components or aberrant catalysis by misfolded mutants underlies a portion of mutant-mediated toxicity.