Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisboa, Portugal.
FEBS Lett. 2012 Jan 2;586(1):7-12. doi: 10.1016/j.febslet.2011.11.019. Epub 2011 Nov 24.
Several neurodegenerative disorders are characterized by the accumulation of proteinaceous inclusions in the central nervous system. These inclusions are frequently composed of a mixture of aggregation-prone proteins. Here, we used a bimolecular fluorescence complementation assay to study the initial steps of the co-aggregation of huntingtin (Htt) and α-synuclein (α-syn), two aggregation-prone proteins involved in Huntington's disease (HD) and Parkinson's disease (PD), respectively. We found that Htt (exon 1) oligomerized with α-syn and sequestered it in the cytosol. In turn, α-syn increased the number of cells displaying aggregates, decreased the number of aggregates per cell and increased the average size of the aggregates. Our results support the idea that co-aggregation of aggregation-prone proteins can contribute to the histopathology of neurodegenerative disorders.
几种神经退行性疾病的特征是中枢神经系统中蛋白包涵体的积累。这些包涵体通常由一组易于聚集的蛋白质组成。在这里，我们使用双分子荧光互补测定法来研究亨廷顿病 (HD) 和帕金森病 (PD) 相关的两种易于聚集的蛋白质——亨廷顿蛋白 (Htt) 和 α-突触核蛋白 (α-syn) 的共聚集的初始步骤。我们发现 Htt（外显子 1）与 α-syn 寡聚化，并将其隔离在细胞质中。反过来，α-syn 增加了显示聚集物的细胞数量，减少了每个细胞中的聚集物数量，并增加了聚集物的平均大小。我们的结果支持这样一种观点，即易于聚集的蛋白质的共聚集可能有助于神经退行性疾病的组织病理学。
