Premature aging-related peripheral neuropathy in a mouse model of progeria.
Premature aging-related peripheral neuropathy in a mouse model of progeria.
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DOI：
10.1016/j.mad.2011.04.010
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发表时间：
2011-08
影响因子：
5.3
通讯作者：
Niedernhofer, Laura J.
中科院分区：
文献类型：
--
作者：
Goss, James R.;Stolz, Donna Beer;Robinson, Andria Rasile;Zhang, Mingdi;Arbujas, Norma;Robbins, Paul D.;Glorioso, Joseph C.;Niedernhofer, Laura J.
周围神经病变是一种常见的与衰老相关的退行性疾病，它会干扰老年人的日常活动，并导致老年人福尔斯跌倒和受伤的风险增加。大多数与年龄相关的周围神经病变的病因是未知的。几种基因组维持机制的遗传缺陷导致组织特异性加速老化，包括神经退行性变。我们检验了一种假设，即由ERCC 1-XPF DNA修复内切酶表达减少引起的XFE早衰样综合征小鼠模型发展为周围神经病变。神经传导研究显示，年轻成年（8周）Ercc 1 −/Δ小鼠的神经功能正常，但20周大的动物出现显著异常。突变小鼠坐骨神经的形态学和超微结构分析显示，在20周龄而不是8周龄时有显著变化。我们的结论是，Ercc 1 −/Δ小鼠具有加速的自发性周围神经变性，模拟衰老相关疾病。这为DNA损伤可以驱动周围神经病变提供了强有力的证据，并为测试治疗提供了快速和新颖的模型。
Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1−/Δ mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1−/Δ mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies.
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DOI：
10.1093/gerona/gln065
发表时间：
2009-02-01
影响因子：
5.1
作者：
Campisi, Judith;Vijg, Jan
通讯作者：
Vijg, Jan
影响因子：
5.3
作者：
Authier, N;Gillet, JP;Coudore, F
通讯作者：
Coudore, F
影响因子：
6
作者：
BOUCHE, P;CATTELIN, F;SIMUNEK, P
通讯作者：
SIMUNEK, P
影响因子：
3.8
作者：
Niedernhofer, Laura J.
通讯作者：
Niedernhofer, Laura J.
影响因子：
5.3
作者：
Ahmad, Anwaar;Robinson, Andria Rasile;Niedernhofer, Laura J.
通讯作者：
Niedernhofer, Laura J.