Identification of the calpain-generated toxic fragment of ataxin-3 protein provides new avenues for therapy of Machado–Joseph disease| Spinocerebellar ataxia type 3,Neuropathology and Applied Neurobiology

当前位置： X-MOL 学术 › Neuropathol. Appl. Neurobiol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Identification of the calpain-generated toxic fragment of ataxin-3 protein provides new avenues for therapy of Machado–Joseph disease| Spinocerebellar ataxia type 3
Neuropathology and Applied Neurobiology ( IF 4.0 ) Pub Date : 2021-07-17 , DOI: 10.1111/nan.12748
Ana Teresa Simões _{1,

2} , Vítor Carmona _{1,

2} , Joana Duarte-Neves _{1,

2} , Janete Cunha-Santos _{1,

2} , Luís Pereira de Almeida _{1,

2,

3}

Affiliation

Machado–Joseph disease (MJD) is the most frequent dominantly inherited cerebellar ataxia worldwide. Expansion of a CAG trinucleotide in the MJD1 gene translates into a polyglutamine tract within ataxin-3, which upon proteolysis may lead to MJD. The aim of this work was to understand the in vivo contribution of calpain proteases to the pathogenesis of MJD. Therefore, we investigated (a) the calpain cleavage sites in ataxin-3 protein, (b) the most toxic ataxin-3 fragment generated by calpain cleavage and (c) whether targeting calpain cleavage sites of mutant ataxin-3 could be a therapeutic strategy for MJD.

中文翻译：

钙蛋白酶产生的ataxin-3蛋白毒性片段的鉴定为马查多-约瑟夫病的治疗提供了新途径| 脊髓小脑性共济失调 3 型

Machado-Joseph 病 (MJD) 是全球最常见的显性遗传性小脑性共济失调。MJD1基因中 CAG 三核苷酸的扩增转化为 ataxin-3 内的聚谷氨酰胺束，在蛋白水解后可能导致 MJD。这项工作的目的是了解体内钙蛋白酶对 MJD 发病机制的贡献。因此，我们研究了（a）ataxin-3 蛋白中的钙蛋白酶切割位点，（b）由钙蛋白酶切割产生的毒性最大的 ataxin-3 片段，以及（c）靶向突变ataxin-3 的钙蛋白酶切割位点是否可以成为一种治疗策略对于 MJD。

更新日期：2021-07-17

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11