Proteomic analysis of the pathogenic domain related to aggregate formation

点击翻译按钮获取中文摘要

We studied on the domain, which related to aggregate formation, especially on raft and polyglutamine aggregate itself. The followings are the results which we obtained in this projects.1.The protein specific raft isolation method was established.2.P62 was identified as a protein, which increased as the polyglutamine aggregates were formed.3.We established isolation method of polyglutamine aggregate without using strong detergent and mass spectrometry analysis was performed to identify aggregate associated proteins(AIP). We found several known and unknown proteins in AIP including ubiquilin, one of the ubiquitin binding proteins.4.We found sodium channel beta subunit 4 as a decrease protein in Huntington disease brain. The beta subunits exist in the raft fraction in the brain.5.Beta subunits are identified as new substrates for both BACE1 and gamma secretase.6.We made transgenic mouse of huntingtin exon1 fused with EGFP to visualize the aggregates.