This invention provides a method for preventing the generation of polyglutamine aggregation of proteins in cells, which provides a method for modulating the expression of a first gene in a cell wherein the first gene is one containing more than 36 CAG trinucleotide repeats and encoding a protein that form polyglutamine-mediated protein aggregation. Suppression of the first gene is achieved by reducing the expression of SPT4 gene or SUPT4H gene. It can also be achieved by inhibiting the formation of a Spt4/Spt5 complex or a Supt4h/Supt5h complex. Also provided a method for identifying an agent useful for modulating the expression and aggregation of CAG-expanded gene product, or treating a polyglutamine disease.本發明係提供一防止細胞內產生多麩醯胺酸(polyglutamine)蛋白質聚集的方法，藉由透過調節細胞內第一基因表現之方法，來達成上述的目的，其中第一基因係含有超過36個CAG三核苷酸重複序列的基因，而該基因會編碼出一蛋白質造成多麩醯胺酸蛋白聚集的產生，因此抑制第一基因的表現即可防止多麩醯胺酸蛋白的聚集。而第一基因的抑制，則可藉由減少SPT4或SUPT4H基因之表現，也可經由抑制Spt4/Spt5或Supt4h/Supt5h複合體之形成而達成。此外，本發明亦提供一方法，作為篩選有效的抑制劑，有助於調控CAG-擴張之基因產物的表現與聚集，並可用於治療多麩醯胺酸之疾病。
