◆A research team led by Professor Teijiro Aso and Assistant Professor Takashi Yasukawa of the Department of Gene Function Analysis in the School of Medicine has discovered a new enzyme complex that is expected to have applications in the development of drugs for Alzheimer's disease.
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A research team led by Professor Teijiro Aso and Assistant Professor Takashi Yasukawa of the Department of Gene Function Analysis in the School of Medicine, in collaboration with Dr. Joan Conaway of the Stowers Institute for Medical Research in the United States,and Professor Toru Terada of the Graduate School of Information Science and Technology at the University of Tokyo, has discovered the NRBP1-ubiquitin ligase, which regulates the degradation of the anti-Alzheimer’s disease factors BRI2 and BRI3—proteins that exhibit three actions: inhibiting the production and aggregation of amyloid-β (Aβ), a causative agent of Alzheimer’s disease, and promoting its degradation.They also revealed that this ubiquitin ligase adopts a heterodimeric structure in which Cul2 and Cul4A bind to the dimerized substrate-recognition protein NRBP1. Furthermore, they confirmed that inhibiting NRBP1 function in neurons increases intracellular levels of BRI2 and BRI3, thereby suppressing Aβ production.
Based on the above, the interaction between NRBP1 and BRI2 and BRI3 is expected to serve as a novel target for the development of fundamental treatments for Alzheimer’s disease. In light of these findings, the research team has begun screening for compounds that inhibit this interaction, with support from the RIKEN Program for Drug Discovery and Medical Technology.