상세정보
Export to Refworks부가기능
To Fold or Not to Fold: The Role of Protein Triage in Dictating Neural Cell Fate following Acute Injury
상세 프로파일
| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | To Fold or Not to Fold: The Role of Protein Triage in Dictating Neural Cell Fate following Acute Injury. |
| 개인저자 | Palubinsky, Amy Marie. |
| 단체저자명 | Vanderbilt University. Neuroscience. |
| 발행사항 | [S.l.]: Vanderbilt University., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 122 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781088341728 |
| 학위논문주기 | Thesis (Ph.D.)--Vanderbilt University, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Gurevich, Eugenia V. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Neuronal protein refolding and degradation in response to stress is largely mediated by the HSP70 chaperone complex and is critical for maintaining cell function and survival. While some components of the triage machinery have been identified, we lack both a fundamental understanding of the triage responses that neurons evoke in response to an acute, ischemic stress and an ability to leverage this response to improve protein triage. In this work we have identified changes in known and novel molecules that are part of the chaperone machinery in response to oxygen and glucose deprivation (OGD) that may represent new targets for therapeutic intervention. We find that immediately following a short period of OGD, neurons endogenously attempt to refold damaged proteins but are unable to maintain these increased folding rates. Using an allosteric modulator of the HSP70 complex, 115-7c, which promotes protein refolding, we were able to improve both neuronal protein and lipid integrity. Additionally, cholesterol biosynthesis, bioenergetic status and membrane architecture were all improved by 115-7c while levels of oxidized and ubiquitinated proteins were decreased. Priming naive neurons with 115-7c mimics the endogenous response to low level stress and neuroprotective effects of ischemic preconditioning (PC) in the absence of new protein synthesis. Taken together with our proteomic and metabolic data, we hypothesize that the endogenous response to acute injury is to promote protein refolding and that pharmacological augmentation of this response will allow neurons to better maintain proteostasis, decrease cell injury and maximize energetic capacity in order to survive ischemic stress. Given that stroke is a leading cause of death worldwide, and that there is currently only one FDA-approved treatment for the ischemic stroke, these data are particularly compelling and warrant continued exploration. |
| 일반주제명 | Neurosciences. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
