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

点击翻译按钮获取中文摘要

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.