Therapeutics development against intellectual disability via structural biology analyses

2015 Fiscal Year Final Research Report

• Project/Area Number: 26640037
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Okazawa Hitoshi 東京医科歯科大学, 難治疾患研究所, 教授 (50261996)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: PQBP1 / スプライシング異常 / 構造生物学 / 遺伝子治療 / 小頭症 / 知的障害 / 神経変性疾患

Outline of Final Research Achievements

RNA splicing is implicated in the molecular pathology of neurological diseases, and the concept of RNA splicing diseases has been proposed. In this project, we focused on PQBP1, which is a representative RNA splicing disease gene, a representative disease gene of intellectual disability (ID), and a neurodegeneration-related gene. We intended to perform structural biology analysis of PQBP1 and develop revolutional therapy. As the results, we elucidated pathomechanisms of PQBP1-linked ID/microcephaly through splicing impairment, developed a gene therapy against this disorder. We also clarified structural basis of nteraction between PQBP1 and U5-15KD.

Free Research Field

神経科学