Functional and dynamic gene expression profiling of polyglutamine

聚谷氨酰胺病是由含有拉长的聚谷氨酰胺链序列的异常蛋白引起的。人们普遍认为突变蛋白的聚集在病理过程中是必不可少的。然而，异常蛋白质在聚集过程中引发的分子事件还没有完全阐明。在这个项目中，我们将基因组学和蛋白质组学应用到这个问题上，并研究了哪些基因和蛋白质在表达中受到影响。简而言之，我们发现不同的疾病基因以神经元类型特异性的方式导致不同的基因和蛋白质表达变化。在此过程中，我们发现了新的聚谷氨酰胺病病理修饰基因，可用于未来分子治疗学的发展。

Polyglutamine diseases are caused by abnormal proteins containing an elongated polyglutamine tract sequence. It is generally believed that aggregation of the mutant proteins is essential for the pathology. However, molecular events induced by abnormal proteins during aggregation process are not fully elucidated. In this project, we applied genomics and proteomics to this question and investigated which genes and proteins are affected in expression. In brief, we found that different disease genes cause different gene and protein expression changes in a neuron type-specific manner. During the process, we found novel modifier genes of polyglutamine disease pathology, which could be used for the future development of molecular therapeutics.