國家衛生研究院 NHRI:Item 3990099045/14573
English  |  正體中文  |  简体中文  |  全文筆數/總筆數 : 12145/12927 (94%)
造訪人次 : 855755      線上人數 : 1383
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/3990099045/14573


    題名: In silico prediction of parkinsonian motor deficits-related neurotoxicants based on the adverse outcome pathway concept
    作者: Kan, HL;Tung, CW;Chang, SE;Lin, YC
    貢獻者: Institute of Biotechnology and Pharmaceutical Research
    摘要: Exposure to neurotoxicants has been associated with Parkinson's disease (PD). Limited by the clinical variation in the signs and symptoms as well as the slow disease progression, the identification of parkinsonian neurotoxicants relies on animal models. Here, we propose an innovative in silico model for the prediction of parkinsonian neurotoxicants. The model was designed based on a validated adverse outcome pathway (AOP) for parkinsonian motor deficits initiated from the inhibition of mitochondrial complex I. The model consists of a molecular docking model for mitochondrial complex I protein to predict the molecular initiating event and a neuronal cytotoxicity Quantitative Structure-Activity Relationships (QSAR) model to predict the cellular outcome of the AOP. Four known PD-related complex I inhibitors and four non-neurotoxic chemicals were utilized to develop the threshold of the models and to validate the model, respectively. The integrated model showed 100% specificity in ruling out the non-neurotoxic chemicals. The screening of 41 neurotoxicants and complex I inhibitors with the model resulted in 16 chemicals predicted to induce parkinsonian disorder through the molecular initiating event of mitochondrial complex I inhibition. Five of them, namely cyhalothrin, deguelin, deltamethrin, diazepam, and permethrin, are cases with direct evidence linking them to parkinsonian motor deficit-related signs and symptoms. The neurotoxicant prediction model for parkinsonian motor deficits based on the AOP concept may be useful in prioritizing chemicals for further evaluations on PD potential.
    日期: 2022-12
    關聯: Archives of Toxicology. 2022 Dec;96(12):3305-3314.
    Link to: http://dx.doi.org/10.1007/s00204-022-03376-1
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0340-5761&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000863221000003
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85139146354
    顯示於類別:[童俊維] 期刊論文

    文件中的檔案:

    檔案 大小格式瀏覽次數
    ISI000863221000003.pdf1401KbAdobe PDF162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