國家衛生研究院 NHRI:Item 3990099045/11294
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 925383      線上人數 : 813
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTU Library IR team.
搜尋範圍 查詢小技巧：
  • 您可在西文檢索詞彙前後加上"雙引號"，以獲取較精準的檢索結果
  • 若欲以作者姓名搜尋，建議至進階搜尋限定作者欄位，可獲得較完整資料
    •  進階搜尋
    主頁 ‧ 登入 ‧ 上傳 ‧ 說明 ‧ 關於NHRI ‧ 管理 到手機版


    請使用永久網址來引用或連結此文件: http://ir.nhri.org.tw/handle/3990099045/11294


    題名: The tale of the tail of MANF: ER calcium homeostasis as a therapeutic target
    作者: Harvey, BK;Trychta, KA;Back, SM;Dossat, AM;Yan, S;Anttila, J;Wu, KJ;Airavaara, M;Wang, Y;Henderson, M
    貢獻者: Center for Neuropsychiatric Research
    摘要: Mesencephalic astrocyte-derived neurotrophic factor (MANF) is an endoplasmic reticulum (ER) stress response protein capable of promoting neuroprotection and neurore-generation. We conducted structure and function studies of the various protein domains of MANF and found the C- terminal tail (ASARTDL) is necessary and sufficient for ER localization. We also found the tail is mediating secretion in response to the depletion of calcium in the ER. ER calcium stores are important for many cellular functions, such as protein folding, lipid metabolism, and signaling pathways. Disruption of ER calcium homeostasis is implicated in multiple neurological diseases, including stroke, Parkinson’s disease, and Alzheimer’s disease. Using the tail of MANF, we developed a secreted ER calcium modulated protein (SERCaMP) to monitor ER calcium depletion in both in vitro and in vivo disease models. We created a Gaussia luciferase (GLuc)-ASARTDL SERCaMP reporter and showed that oxygenglucose deprivation caused ER calcium depletion and decreased cell viability. Treatment with the ryanodine receptor antagonist dantrolene attenuated secretion of our reporter and increased cell viability in vitro. Intracranial adenoassociated virus (AAV)-GLuc-SERCaMP-injected rats showed evidence of ER calcium depletion following occlusion of the middle cerebral artery and dantrolene treatment reduced the infarction volume. Lastly, we developed a high throughput screen based on our GLuc-SERCaMP reporter and identified novel drugs for stabilizing ER calcium and improving recovery from oxygen-glucose deprivation. Our data support a model in which stroke causes ER calcium depletion and suggests that dantrolene can be used to reduce ER calcium depletion and improve the outcome from ischemic damage.
    日期: 2018-04
    關聯: Cell Transplantation. 2018 Apr;27(4, Suppl. SI):696.
    Link to: https://doi.org/10.1177/0963689718765742
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0963-6897&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000438559500041
    顯示於類別:[其他] 會議論文/會議摘要

    文件中的檔案:

    檔案 大小格式瀏覽次數
    ISI000438559500041.pdf35KbAdobe PDF286檢視/開啟


    在NHRI中所有的資料項目都受到原著作權保護.

    TAIR相關文章

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - 回饋