FOXO transcription factors as therapeutic targets in human diseases.

TitleFOXO transcription factors as therapeutic targets in human diseases.
Publication TypeJournal Article
Year of Publication2022
AuthorsOrea-Soufi A, Paik J, Bragan├ža J, Donlon TA, Willcox BJ, Link W
JournalTrends Pharmacol Sci
Volume43
Issue12
Pagination1070-1084
Date Published2022 Dec
ISSN1873-3735
KeywordsForkhead Transcription Factors, Humans, Longevity
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.

DOI10.1016/j.tips.2022.09.010
Alternate JournalTrends Pharmacol Sci
PubMed ID36280450
Grant ListR01 CA219957 / CA / NCI NIH HHS / United States
R56 AG048284 / AG / NIA NIH HHS / United States
U01 AG019349 / AG / NIA NIH HHS / United States
R01 AG027060 / AG / NIA NIH HHS / United States
R01 AG038707 / AG / NIA NIH HHS / United States
P20 GM125526 / GM / NIGMS NIH HHS / United States
P01 CA214274 / CA / NCI NIH HHS / United States
Related Faculty: 
Ji-Hye Paik, Ph.D.

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