Huntington’s disease (HD) is a severe neurodegenerative disorder caused by poly Q repeat expansion in the Huntingtin (Htt) gene. While the Htt amyloid aggregates are known to affect many cellular processes, their role in translation has not been addressed. Here we report that pathogenic Htt expression causes a protein synthesis deficit in cells. We find a functional prion-like protein, the translation regulator Orb2, to be sequestered by Htt aggregates in cells. Co-expression of Orb2 can partially rescue the lethality associated with poly Q expanded Htt. These findings can be relevant for HD as human homologs of Orb2 are also sequestered by pathogenic Htt aggregates. Our work suggests that translation dysfunction is one of the contributors to the pathogenesis of HD and new therapies targeting protein synthesis pathways might help to alleviate disease symptoms.

中文翻译：

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细胞翻译调节与毒性亨廷顿蛋白有关的作用。

亨廷顿舞蹈病（HD）是由Huntingtin（Htt）基因中的poly Q重复扩增引起的严重神经退行性疾病。虽然已知Htt淀粉样蛋白聚集物会影响许多细胞过程，但尚未解决它们在翻译中的作用。在这里我们报告致病性Htt表达导致细胞中蛋白质合成不足。我们发现功能性病毒样蛋白，翻译调节器Orb2，被细胞中的Htt聚集体隔离。共表达Orb2可以部分挽救与聚Q扩展Htt相关的杀伤力。这些发现可能与HD相关，因为Orb2的人类同源物也被致病性Htt聚集体隔离。