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  • 09월 04일 17시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제114회 대한화학회 학술발표회, 총회 및 기기전시회 안내 Modulating Intracellular Protein Degradation and Its Implications in Neurodegenerative Diseases

2014년 9월 1일 19시 02분 31초
BIO1-2 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
목 09시 : 20분
생명화학 - Neurodegenerative Diseases in Life Chemistry
저자 및
경희대학교 응용화학과, Korea

Rates of proteolysis are a function of cell’s physiological state and are controlled differentially for individual proteins, affecting a variety of regulatory pathways both in normal and pathological conditions. The ubiquitin-proteasome system (UPS) is responsible for the degradation of most intracellular proteins in eukaryotes. As our knowledge of biological processes in the systems has grown for the last 30 years, so have the ties between the systems and various human diseases including cancers, metabolic diseases, and neurodegenerative diseases. In this presentation, I intend to provide an example of studies which were involved in small-molecule inhibitor/activator development in the ubiquitin-proteasome system through rational design and high-throughput screening, and its application to modulate its biochemical and functional outputs. Moreover, we would like to emphasize that purified proteasomes can be directly transported into cells through mesoporous silica nanoparticle-mediated endocytosis. Proteasomes that were loaded onto nanoparticles through noncovalent interactions between poly-histidine tags and nickel ions fully retained their proteolytic activity. Cells treated with exogenous proteasomes were more efficient in degrading overexpressed human tau than endogenous proteasomal substrates, resulting in decreased levels of tau aggregates. Moreover, exogenous proteasome delivery significantly promoted cell survival against proteotoxic stress caused by tau and reactive oxygen species. These data demonstrate that increasing cellular proteasome activity through the direct delivery of purified proteasomes may be an effective strategy for reducing cellular levels of proteotoxic proteins.