期刊
TRENDS IN PHARMACOLOGICAL SCIENCES
卷 43, 期 12, 页码 1070-1084出版社
CELL PRESS
DOI: 10.1016/j.tips.2022.09.010
关键词
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资金
- Spanish Ministry of Science, Innovation, and Universities [RTI2018-094629-BI00]
- Kuakini Medical Center
- US National Institutes of Health [N01-AG-42149, 5U01AG019349-05, 5R01AG027060, 5R01AG038707, 1P20GM125526-01A1]
- National Heart, Lung, and Blood Institute [N01-HC-05102]
- National Cancer Institute [P01CA214274]
- National Institute of Aging [R56AG048284]
- Fundacao para a Ciencia e Tecnologia (FCT)
- Comissao de Coordenacao e Desenvolvimento Regional do Algarve (CCDR Algarve) [ALG-01-0145-FEDER-28044, PTDC/BTM-TEC/28044/2017, ALG-01-0145-FEDER-072586, 072586]
- STRATAGEM COST Action [CA17104]
FOXO proteins are important transcription factors involved in cellular stress adaptation and tumor suppression. Modulating the activity and function of FOXO proteins has potential clinical applications in treating various diseases.
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 under-standing 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.
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