Neural Regeneration Research ›› 2021, Vol. 16 ›› Issue (10): 1944-1949.doi: 10.4103/1673-5374.308075

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Proteolysis targeting chimera technology: a novel strategy for treating diseases of the central nervous system

Ke Ma2, #, Xiao-Xiao Han1, #, Xiao-Ming Yang1, Song-Lin Zhou1, *   

  1. 1Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, 
    Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China; 2College of Life Science, Nantong University, Nantong, Jiangsu Province, China
  • Online:2021-10-15 Published:2021-03-18
  • Contact: Song-Lin Zhou, PhD, songlin.zhou@ntu.edu.cn.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81870975 (to SLZ); and the Nantong Science and Technology Innovation Program, China, No. JC2019028 (to XMY).

Abstract: Neurological diseases such as stroke, Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease are among the intractable diseases for which appropriate drugs and treatments are lacking. Proteolysis targeting chimera (PROTAC) technology is a novel strategy to solve this problem. PROTAC technology uses the ubiquitin-protease system to eliminate mutated, denatured, and harmful proteins in cells. It can be reused, and utilizes the protein destruction mechanism of the cells, thus making up for the deficiencies of traditional protein degradation methods. It can effectively target and degrade proteins, including proteins that are difficult to identify and bind. Therefore, it has extremely important implications for drug development and the treatment of neurological diseases. At present, the targeted degradation of mutant BTK, mHTT, Tau, EGFR, and other proteins using PROTAC technology is gaining attention. It is expected that corresponding treatment of nervous system diseases can be achieved. This review first focuses on the recent developments in PROTAC technology in terms of protein degradation, drug production, and treatment of central nervous system diseases, and then discusses its limitations. This review will provide a brief overview of the recent application of PROTAC technology in the treatment of central nervous system diseases. 

Key words: Alzheimer’s disease, disease treatment, drug development, Huntington’s disease, proteolysis targeting chimera, stroke, targeted degradation