PROTACs and Other Chemical Protein Degradation Technologies for the Treatment of Neurodegenerative Disorders

Angew Chem Int Ed Engl. 2021 Feb 15;60(7):3346-3354. doi: 10.1002/anie.202004746. Epub 2020 Aug 18.


Neurodegenerative disorders (NDs) are a group of diseases that cause neural cell damage, leading to motility and/or cognitive dysfunctions. One of the causative agents is misfolded protein aggregates, which are considered as undruggable in terms of conventional tools, such as inhibitors and agonists/antagonists. Indeed, there is currently no FDA-approved drug for the causal treatment of NDs. However, emerging technologies for chemical protein degradation are opening up the possibility of selective elimination of target proteins through physiological protein degradation machineries, which do not depend on the functions of the target proteins. Here, we review recent efforts towards the treatment of NDs using chemical protein degradation technologies, and we briefly discuss the challenges and prospects.

Keywords: PROTACs; autophagy inducers; drug discovery; neurodegenerative disorders; protein degradation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Humans
  • Neurodegenerative Diseases / drug therapy*
  • Neurodegenerative Diseases / metabolism
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology*
  • Protein Aggregates / drug effects
  • Proteins / agonists*
  • Proteins / antagonists & inhibitors*
  • Proteins / metabolism
  • Proteolysis / drug effects*


  • Neuroprotective Agents
  • Protein Aggregates
  • Proteins