First evidence of pathogenicity of V234I mutation of hVAPB found in Amyotrophic Lateral Sclerosis
First evidence of pathogenicity of V234I mutation of hVAPB found in Amyotrophic Lateral Sclerosis
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DOI：
10.1016/j.bbrc.2014.04.102
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发表时间：
2014-05-23
影响因子：
3.1
通讯作者：
Sengupta, Soma
中科院分区：
文献类型：
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作者：
Chattopadhyay, Dhrubajyoti;Sengupta, Soma
肌萎缩侧索硬化症是一种运动神经退行性疾病，其特征是运动神经元进行性丧失，继而瘫痪，最终死亡。在人类中，VAMP相关蛋白B(VAPB)是ALS8家族性形式的致病基因。以前的研究表明，这种形式的ALS中存在hVAPB的P56S和T46I点突变。最近，在一个ALS家族性病例中发现了另一种突变，即hVAPB的V234I。这是我们第一次发现V234I-VAPB不像VAPB的另外两个突变体那样形成聚集体，并且定位不同于野生型VAPB。它诱导泛素聚集，继而导致细胞死亡。我们认为，V234I-VAPB虽然在各种神经退行性疾病中不具有不同突变的典型聚集特性，但仍具有ALS的特征。(C)2014 Elsevier Inc.保留所有权利。
Amyotrophic Lateral Sclerosis is a motor neurodegenerative disease which is characterized by progressive loss of motor neurons followed by paralysis and eventually death. In human, VAMP-associated protein B (VAPB) is the causative gene of the familial form of ALS8. Previous studies have shown that P56S and T46I point mutations of hVAPB are present in this form of ALS. Recently, another mutation, V234I of hVAPB was found in one familial case of ALS. This is the first study where we have shown that V234I-VAPB does not form aggregate like other two mutants of VAPB and localizes differently than the wild type VAPB. It induces Ubiquitin aggregation followed by-cell death. We propose that V234I-VAPB exhibits the characteristics of ALS in spite of not having the typical aggregation property of different mutations in various neurodegenerative diseases. (C) 2014 Elsevier Inc. All rights reserved.