Activation and inhibition of sirtuins: From bench to bedside.

Autor: Fiorentino F; Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy., Fabbrizi E; Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy., Mai A; Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.; Pasteur Institute, Cenci-Bolognetti Foundation, Sapienza University of Rome, Rome, Italy., Rotili D; Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
Jazyk: angličtina
Zdroj: Medicinal research reviews [Med Res Rev] 2024 Aug 31. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1002/med.22076
Abstrakt: The sirtuin family comprises seven NAD + -dependent enzymes which catalyze protein lysine deacylation and mono ADP-ribosylation. Sirtuins act as central regulators of genomic stability and gene expression and control key processes, including energetic metabolism, cell cycle, differentiation, apoptosis, and aging. As a result, all sirtuins play critical roles in cellular homeostasis and organism wellness, and their dysregulation has been linked to metabolic, cardiovascular, and neurological diseases. Furthermore, sirtuins have shown dichotomous roles in cancer, acting as context-dependent tumor suppressors or promoters. Given their central role in different cellular processes, sirtuins have attracted increasing research interest aimed at developing both activators and inhibitors. Indeed, sirtuin modulation may have therapeutic effects in many age-related diseases, including diabetes, cardiovascular and neurodegenerative disorders, and cancer. Moreover, isoform selective modulators may increase our knowledge of sirtuin biology and aid to develop better therapies. Through this review, we provide critical insights into sirtuin pharmacology and illustrate their enzymatic activities and biological functions. Furthermore, we outline the most relevant sirtuin modulators in terms of their modes of action, structure-activity relationships, pharmacological effects, and clinical applications.
(© 2024 The Author(s). Medicinal Research Reviews published by Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: