Molecular therapy for the polyglutamine diseases using a novel brain delivery method of aggregate inhibitor peptides

多聚谷氨酰胺（PolyQ）疾病是由脑中蛋白质聚集引起的神经系统疾病。我们先前鉴定了QBP1，一种抑制PolyQ疾病聚集的分子。然而，对于QBP1作为治疗的实际使用，其向大脑的低效递送是一个问题。在这项研究中，为了改善QBP1的大脑递送，我们（1）筛选PTD，PTD是允许将各种分子递送到细胞中的序列，使QBP1能够在大脑中递送，以及（2）为了减小QBP1的大小，我们分析了QBP1的哪一部分是其活性所必需的。结果，我们（1）发现一些PTDs与QBP 1的融合似乎增强了其脑递送，并且（2）确定了其治疗效果所需的QBP 1部分。

The polyglutamine (PolyQ) diseases are neurological diseases caused by protein aggregation in the brain. We previously identified QBP1, a molecule that inhibits PolyQ disease aggregation. However, for actual use of QBP1 as a therapy, its inefficient delivery to the brain was a problem. In this study, to improve brain delivery of QBP1, we (1) screened for PTDs, which are sequences that allow the delivery of various molecules into cells, that enable brain delivery of QBP1, and (2) to decrease the size of QBP1, we analyzed which part of QBP1 is required for its activity. As a result, we (1) found that fusion of some PTDs to QBP1 appears to enhance its brain delivery, and (2) determined the part of QBP1 required for its therapeutic effect.