To understand the pathogenesis of many diseases attributed to protein toxicity such as polyglutamine (polyQ) diseases, it is very crucial to determine how these toxic disease proteins interact and trap their numerous targets. However, in polyQ diseases, details of required features for their interaction with targets remain largely unknown. Here, we identified what features are necessity for interaction between polyQ and targets, and how target proteins have an effect on polyQ aggregate formation. We visualized the interaction between pathogenic polyQ proteins and Q-rich possible target proteins in neurons, which is predicted on the Q-Q based protein interaction occurring in pathogenic polyQ-containing proteins for their self-oligomerization/aggregation. Furthermore, we checked whether the interaction of pathogenic polyQ proteins with targets can be modulated through designed strategies such as using a structural inhibitor molecule. Through this study, we established the model system to study the modes of interaction between pathogenic polyQ and Q-rich target proteins and aim to prove the possibility of target proteins accelerating aggregate formation by acting as glue. ⓒ 2016 DGIST
Table Of Contents
Ⅰ. INTRODUCTION 1 -- Ⅱ. MATERIALS AND METHOD 3 -- 2.1 Fly stocks 3 -- 2.2 Identification of Q-rich proteins 3 -- 2.3 Immunostaining 4 -- 2.4 Statistical analysis for significant test 5 -- 2.5 Microscope Imaging 5 -- Ⅲ. RESULT 6 -- 3.1 Pathogenic polyQ proteins interact with Q-rich polyQ proteins 6 -- 3.2 Possible target proteins in the cell and Co-lacaliztion between possible Q-rich target proteins and pathogenic polyQ proteins 8 -- 3.3 Overexpressed target proteins with polyQ proteins increased aggregation form 10 -- 3.4 QBP1 prevent interaction between polyQ proteins and target proteins 11 -- 3.5 RNA interference of target proteins decreased polyQ protein (Htt) aggregate numbers 13 -- IV. DISCUSSION 14 -- V. Figures and tables 15 -- VI. References 39 -- VII. Summary in Korean 43