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.
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
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DOI: 10.1021/acs.jmedchem.2c00844 PMID: 36006861
摘要 Ai翻译
Keywords:targeted protein degradation
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