The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease

Drug Discov Today. 2021 Jan;26(1):218-228. doi: 10.1016/j.drudis.2020.10.015. Epub 2020 Oct 24.

Abstract

Apurinic/apyrimidinic (AP) endonuclease-reduction/oxidation factor 1 (APE1/Ref-1, also called APE1) is a multifunctional enzyme with crucial roles in DNA repair and reduction/oxidation (redox) signaling. APE1 was originally described as an endonuclease in the Base Excision Repair (BER) pathway. Further study revealed it to be a redox signaling hub regulating critical transcription factors (TFs). Although a significant amount of focus has been on the role of APE1 in cancer, recent findings support APE1 as a target in other indications, including ocular diseases [diabetic retinopathy (DR), diabetic macular edema (DME), and age-related macular degeneration (AMD)], inflammatory bowel disease (IBD) and others, where APE1 regulation of crucial TFs impacts important pathways in these diseases. The central responsibilities of APE1 in DNA repair and redox signaling make it an attractive therapeutic target for cancer and other diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • DNA Repair*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism*
  • Drug Discovery
  • Humans
  • Molecular Targeted Therapy / methods
  • Oxidation-Reduction / drug effects
  • Signal Transduction / drug effects
  • Transcription Factors / metabolism

Substances

  • Transcription Factors
  • APEX1 protein, human
  • DNA-(Apurinic or Apyrimidinic Site) Lyase