TDP-43 mutation in familial amyotrophic lateral sclerosis
TDP-43 mutation in familial amyotrophic lateral sclerosis
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DOI：
10.1002/ana.21392
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发表时间：
2008-04-01
影响因子：
11.2
通讯作者：
Onodera, Osamu
中科院分区：
文献类型：
--
作者：
Yokoseki, Akio;Shiga, Atsushi;Onodera, Osamu
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病。越来越多的证据表明，43 kDa的TAR-DNA结合蛋白（TDP-43）是ALS和额颞叶变性的致病蛋白。我们以前报道了一个家族性ALS与Bumina体和TDP-43阳性绞样包涵体在下运动神经元，这些发现是无法区分的散发性ALS。在一个家族的两代中的三个受影响的个体中，我们发现TDP-43中位置1028处的单个碱基对从A变为G，这导致位置343处的Gln-to-Arg取代。我们的发现为ALS的分子发病机制提供了新的见解。
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder. Accumulating evidence has shown that 43kDa TAR-DNA-binding protein (TDP-43) is the disease protein in ALS and frontotemporal lobar degeneration. We previously reported a familial ALS with Bumina bodies and TDP-43-positive skein-like inclusions in the lower motor neurons; these findings are indistinguishable from those of sporadic ALS. In three affected individuals in two generations of one family, we found a single base-pair change from A to G at position 1028 in TDP-43, which resulted in a Gln-to-Arg substitution at position 343. Our findings provide a new insight into the molecular pathogenesis of ALS.