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Review Journal of medicinal chemistry. 2022 Sep 8;65(17):11454-11477. doi: 10.1021/acs.jmedchem.2c00844 Q16.82025

Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy

靶向蛋白降解在神经退行性疾病治疗中的进展与挑战 翻译改进

Yingxu Fang  1  2, Jiaxing Wang  3, Min Zhao  1  2  4, Qinwen Zheng  1, Changyu Ren  5, Yuxi Wang  1  2  4, Jifa Zhang  1  2  4

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作者单位

  • 1 Joint Research Institution of Altitude Health, Department of Respiratory and Critical Care Medicine, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
  • 2 Targeted Tracer Research and Development Laboratory, Institute of Respiratory Health, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
  • 3 Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States.
  • 4 Tianfu Jincheng Laboratory, Chengdu 610041, Sichuan, China.
  • 5 Department of Pharmacy, Chengdu Fifth People's Hospital, Chengdu 611130, Sichuan, China.
  • DOI: 10.1021/acs.jmedchem.2c00844 PMID: 36006861

    摘要 Ai翻译

    Neurodegenerative diseases (NDs) are currently incurable diseases that cause progressive degeneration of nerve cells. Many of the disease-causing proteins of NDs are "undruggable" for traditional small-molecule inhibitors (SMIs). None of the compounds that attenuated the amyloid-β (Aβ) accumulation process have entered clinical practice, and many phase III clinical trials of SMIs for Alzheimer's disease (AD) have failed. In recent years, emerging targeted protein degradation (TPD) technologies such as proteolysis-targeting chimeras (PROTACs), lysosome-targeting chimaeras (LYTACs), and autophagy-targeting chimeras (AUTACs) with TPD-assistive technologies such as click-formed proteolysis-targeting chimeras (CLIPTACs) and deubiquitinase-targeting chimera (DUBTAC) have developed rapidly. In vitro and in vivo experiments have also confirmed that TPD technology can target the degradation of ND pathogenic proteins, bringing hope for the treatment of NDs. Herein, we review the latest TPD technologies, introduce their targets and technical characteristics, and discuss the emerging TPD technologies with potential in ND research, with the hope of providing a new perspective for the development of TPD technology in the NDs field.

    Keywords:targeted protein degradation

    Copyright © Journal of medicinal chemistry. 中文内容为AI机器翻译,仅供参考!

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    期刊名:Journal of medicinal chemistry

    缩写:J MED CHEM

    ISSN:0022-2623

    e-ISSN:1520-4804

    IF/分区:6.8/Q1

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    Progress and Challenges in Targeted Protein Degradation for Neurodegenerative Disease Therapy