4.6 Review

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

Journal

NEURAL REGENERATION RESEARCH
Volume 16, Issue 10, Pages 1944-1949

Publisher

WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/1673-5374.308075

Keywords

Alzheimer's disease; disease treatment; drug development; Huntington's disease; proteolysis targeting chimera; stroke; targeted degradation

Funding

  1. National Natural Science Foundation of China [81870975]
  2. Nantong Science and Technology Innovation Program, China [JC2019028]

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PROTAC technology is a novel strategy that targets and degrades disease-related proteins in cells using the protein degradation mechanism, which has important implications for the treatment of neurological diseases. Currently, attention is being drawn to utilizing PROTAC technology for the treatment of nervous system diseases with expectations of significant progress.
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.

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