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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila
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A cell-based assay for aggregation inhibitors as therapeutics of polyglutamine-repeat disease and validation in Drosophila

机译：一种基于细胞的聚集抑制剂作为多谷氨酰胺重复性疾病治疗剂的方法，并在果蝇中进行验证

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摘要

The formation of polygIutamine-con taining aggregates and inclusions are hallmarks of pathogenesis in Huntington's disease that can be recapitulated in model systems. Although the contribution of inclusions to pathogenesis is unclear, cell-based assays can be used to screen for chemical compounds that affect aggregation and may provide therapeutic benefit. We have developed inducible PC12 cell-culture models to screen for loss of visible aggregates. To test the validity of this approach, compounds that inhibit aggregation in the PC12 cell-based screen were tested in a Drosophila model of polyglutamine-repeat disease. The disruption of aggregation in PC12 cells strongly correlates with suppression of neu-ronal degeneration in Drosophila. Thus, the engineered PC12 cells coupled with the Drosophila model provide a rapid and effective method to screen and validate compounds.
机译：含有聚谷氨酰胺的聚集体和内含物的形成是亨廷顿氏病发病机理的标志，可以在模型系统中概括。尽管尚不清楚内含物对发病机制的贡献，但基于细胞的测定法可用于筛选影响聚集并可能提供治疗益处的化合物。我们已经开发出诱导型PC12细胞培养模型，以筛选可见聚集体的损失。为了测试该方法的有效性，在多谷氨酰胺重复性疾病的果蝇模型中测试了在PC12细胞筛选中抑制聚集的化合物。 PC12细胞聚集的破坏与果蝇中神经元变性的抑制密切相关。因此，结合果蝇模型的工程PC12细胞提供了一种快速有效的方法来筛选和验证化合物。

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