자료유형 | 학위논문 |
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서명/저자사항 | The Discovery and Characterization of Small Molecule 20s Proteasome Activators: Implications in Proteostasis Disorders. |
개인저자 | Njomen, Evert. |
단체저자명 | Michigan State University. Chemistry - Doctor of Philosophy. |
발행사항 | [S.l.]: Michigan State University., 2019. |
발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
형태사항 | 205 p. |
기본자료 저록 | Dissertations Abstracts International 81-02B. Dissertation Abstract International |
ISBN | 9781085615808 |
학위논문주기 | Thesis (Ph.D.)--Michigan State University, 2019. |
일반주기 |
Source: Dissertations Abstracts International, Volume: 81-02, Section: B.
Advisor: Tepe, Jetze . |
이용제한사항 | This item must not be sold to any third party vendors. |
요약 | Maintenance of proteome fidelity is required to preserve the health of an organism in defiance of developmental fluxes, environmental insults, infectious diseases, and the challenges of aging. This crucial role is the responsibility of the proteostasis (protein homeostasis) network, a multicomponent and unified system involving protein synthesis, folding, and degradation. The degradation system is regulated by the proteasome and the autophagy pathways. These proteolytic systems have thus emerged as therapeutic targets for numerous proteostasis disorders. However, their therapeutic regulation is only feasible if there is a fine understanding of how they function, and the mechanisms of crosstalk underlying their cooperative nature. After more than three decades since the discovery of the proteasome, there is still so much to be known about this exquisite enzyme. Proteolysis by the proteasome could be 20S- or 26S-mediated and may or may not be ubiquitin-dependent. The goal of this dissertation was to discover and characterize small molecules that allow for the decoding of 20S-mediated proteolysis and its role in the regulation of autophagy, with the hope of finding new vulnerabilities for proteostasis drug discovery.In this endeavor, two classes of 20S proteasome activators |
일반주제명 | Chemistry. Pharmacology. Toxicology. |
언어 | 영어 |
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