FOXO transcription factors as therapeutic targets in human diseases. Review uri icon

Overview

abstract

  • Forkhead box (FOX)O proteins are transcription factors (TFs) with four members in mammals designated FOXO1, FOXO3, FOXO4, and FOXO6. FOXO TFs play a pivotal role in the cellular adaptation to diverse stress conditions. FOXO proteins act as context-dependent tumor suppressors and their dysregulation has been implicated in several age-related diseases. FOXO3 has been established as a major gene for human longevity. Accordingly, FOXO proteins have emerged as potential targets for the therapeutic development of drugs and geroprotectors. In this review, we provide an overview of the most recent advances in our understanding of FOXO regulation and function in various pathological conditions. We discuss strategies targeting FOXOs directly or by the modulation of upstream regulators, shedding light on the most promising intervention points. We also reveal the most relevant clinical indications and discuss the potential, trends, and challenges of modulating FOXO activity for therapeutic purposes.

publication date

  • October 21, 2022

Research

keywords

  • Forkhead Transcription Factors
  • Longevity

Identity

Scopus Document Identifier

  • 85140333614

Digital Object Identifier (DOI)

  • 10.1016/j.tips.2022.09.010

PubMed ID

  • 36280450

Additional Document Info

volume

  • 43

issue

  • 12