FoxO3 and oxidative stress: a multifaceted role in cellular adaptation

J Mol Med (Berl). 2023 Feb;101(1-2):83-99. doi: 10.1007/s00109-022-02281-5. Epub 2023 Jan 4.

Abstract

Oxidative stress is a major cause of morbidity and mortality in human health and disease. In this review, we focus on the Forkhead Box (Fox) subclass O3 (FoxO3), an extensively studied transcription factor that plays a pleiotropic role in a wide range of physiological and pathological processes by regulating multiple gene regulatory networks involved in the modulation of numerous aspects of cellular metabolism, including fuel metabolism, cell death, and stress resistance. This review will also focus on regulatory mechanisms of FoxO3 expression and activity, such as crucial post-translational modifications and non-coding RNAs. Moreover, this work discusses and evidences some pathways to how this transcription factor and reactive oxygen species regulate each other, which may lead to the pathogenesis of various types of diseases. Therefore, in addition to being a promising therapeutic target, the FoxO3-regulated signaling pathways can also be used as reliable diagnostic and prognostic biomarkers and indicators for drug responsiveness.

Keywords: Pathological processes; Reactive oxygen species; Regulatory networks; Therapeutic target.

Publication types

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

MeSH terms

  • Forkhead Box Protein O3* / metabolism
  • Forkhead Transcription Factors* / metabolism
  • Gene Expression Regulation
  • Humans
  • Oxidative Stress* / genetics
  • Signal Transduction

Substances

  • Forkhead Box Protein O3
  • Forkhead Transcription Factors
  • FOXO3 protein, human