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A study on novel inhibitor of Tau aggregation and membrane binding of Tau aggregates : 화합물을 이용한 Tau 응집 조절과 응집된 Tau 에 세포막 결합에 대한 연구

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Authors
최지현
Advisor
박상현
Major
자연과학대학 생명과학부
Issue Date
2018-08
Publisher
서울대학교 대학원
Description
학위논문 (박사)-- 서울대학교 대학원 : 자연과학대학 생명과학부, 2018. 8. 박상현.
Abstract
Tau is an intracellular microtubule-associated protein that stabilizes microtubules. Under normal physiological conditions, Tau is a naturally unfolded and highly soluble protein. However, in Alzheimers disease, Tau is hyperphosphorylated and aggregated into intracellular neurofibrillary tangles (NFT). Aggregated Tau can transmit into adjacent cells and induce aggregation. This prion-like Tau propagation is an important mechanism for disease progression. Therefore, inhibition of aggregation and transmission of Tau can provide an important strategy for therapeutic agents of Alzheimers disease. In this study, we screened six novel inhibitors for Tau aggregation and designed one novel inhibitor based on the screened compounds structures. A total of 62 compounds were synthesized and 32 compounds efficiently inhibited Tau aggregation. Additionally, we developed a new measuring method for membrane binding of aggregated Tau. To measure aggregation-dependent membrane binding, fluorescence labeled Tau was utilized. Tau bound to living cell membranes by aggregation in a dose-dependent manner. In addition, using aggregation inhibitor, we confirmed that this method could be a convenient cell-based approach for validation or screening of membrane binding inhibitors.
Language
English
URI
https://hdl.handle.net/10371/143011
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College of Natural Sciences (자연과학대학)Dept. of Biological Sciences (생명과학부)Theses (Ph.D. / Sc.D._생명과학부)
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