Accumulation of TDP-43 and α-actin in an amyotrophic lateral sclerosis patient with the K17I ANG mutation
Accumulation of TDP-43 and α-actin in an amyotrophic lateral sclerosis patient with the K17I ANG mutation
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DOI：
10.1007/s00401-009-0545-9
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发表时间：
2009-10-01
影响因子：
12.7
通讯作者：
Duyckaerts, Charles
中科院分区：
文献类型：
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作者：
Seilhean, Danielle;Cazeneuve, Cecile;Duyckaerts, Charles
在我们先前发表的具有神经元核内蛋白内含物的ALS病例中，已经鉴定了编码血管生成素的ANG基因中的K17 I突变（Seilhean等，Acta Neuropathol 108：81-87，2004）。这些夹杂物的平滑肌α-肌动蛋白，但不为血管生成素的免疫反应。此外，它们没有被标记的抗TDP-43抗体，而众多的细胞质包涵体免疫反应的泛素，p62和TDP-43检测在少突胶质细胞和神经元在中枢神经系统的各个区域。此外，在观察到严重脂肪变性的肝脏中，平滑肌α-肌动蛋白的表达增加。这是第一个神经病理学描述的情况下，ANG突变。已知血管生成素与肌动蛋白相互作用。与ALS发病机制中涉及的其他蛋白质如senataxin、TDP-43和FUS/TLS一样，它在RNA成熟中起作用。
A K17I mutation in the ANG gene encoding angiogenin has been identified in a case that we previously published as ALS with neuronal intranuclear protein inclusions (Seilhean et al. in Acta Neuropathol 108:81-87, 2004). These inclusions were immunoreactive for smooth muscle alpha-actin but not for angiogenin. Moreover, they were not labeled by anti-TDP-43 antibodies, while numerous cytoplasmic inclusions immunoreactive for ubiquitin, p62 and TDP-43 were detected in both oligodendrocytes and neurons in various regions of the central nervous system. In addition, expression of smooth muscle alpha-actin was increased in the liver where severe steatosis was observed. This is the first neuropathological description of a case with an ANG mutation. Angiogenin is known to interact with actin. Like other proteins involved in ALS pathogenesis, such as senataxin, TDP-43 and FUS/TLS, it plays a role in RNA maturation.