期刊
LIFE-BASEL
卷 11, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/life11070607
关键词
neurodegenerative disease; protein degradation; drug design; ubiquitin-proteasome system; autophagy; protac
资金
- National Research Foundation of Korea [NRF-2018R1DA1A 02086100, 2020R1A6A1A03043708]
- National Research Foundation of Korea [2020R1A6A1A03043708] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Neurodegenerative diseases are characterized by dysfunction of cognition and mobility, often caused by aggregates of misfolded proteins. Recently, targeted protein degradation using small molecules has emerged as a promising new therapeutic approach for these challenging diseases. Various technologies, such as molecular glues, have shown success in degrading disease-related proteins and may hold potential for the treatment of neurodegenerative diseases caused by protein aggregation.
Neurodegenerative diseases, including Alzheimer's disease, Huntington's disease, and Parkinson's disease, are a class of diseases that lead to dysfunction of cognition and mobility. Aggregates of misfolded proteins such as beta-amyloid, tau, alpha-synuclein, and polyglutamates are known to be among the main causes of neurodegenerative diseases; however, they are considered to be some of the most challenging drug targets because they cannot be modulated by conventional small-molecule agents. Recently, the degradation of target proteins by small molecules has emerged as a new therapeutic modality and has garnered the interest of the researchers in the pharmaceutical industry. Bifunctional molecules that recruit target proteins to a cellular protein degradation machinery, such as the ubiquitin-proteasome system and autophagy-lysosome pathway, have been designed. The representative targeted protein degradation technologies include molecular glues, proteolysis-targeting chimeras, hydrophobic tagging, autophagy-targeting chimeras, and autophagosome-tethering compounds. Although these modalities have been shown to degrade many disease-related proteins, such technologies are expected to be potentially important for neurogenerative diseases caused by protein aggregation. Herein, we review the recent progress in chemical-mediated targeted protein degradation toward the discovery of drugs for neurogenerative diseases.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据