Journal
TRENDS IN PHARMACOLOGICAL SCIENCES
Volume 40, Issue 12, Pages 1021-1039Publisher
ELSEVIER SCIENCE LONDON
DOI: 10.1016/j.tips.2019.09.003
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Funding
- European Regional Development Fund (FEDER), through Programa Operacional Factores de Competitividade COMPETE2020
- Fundacao para a Ciencia e a Tecnologia (FCT) [POCI-01-0145-FEDER-007440, UID/NEU/04539/2013, UID/NEU/04539/2019, POCI-01-0145-FEDER-030167, POCI-01-0145-FEDER-031712, PTDC/SAU-NUT/31712/2017, CENTRO-01-0145-FEDER-000012-HealthyAging]
- FCT [SFRH/BD/121923/2016]
- Fundação para a Ciência e a Tecnologia [PTDC/SAU-NUT/31712/2017, SFRH/BD/121923/2016] Funding Source: FCT
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Sirtuins (SIRT1-7), a class of NAD(+)-dependent deacylases, are central regulators of metabolic homeostasis and stress responses. While numerous salutary effects associated with sirtuin activation, especially SIRT1, are well documented, other reports show health benefits resulting from sirtuin inhibition. Furthermore, conflicting findings have been obtained regarding the patho-physiological role of specific sirtuin isoforms, suggesting that sirtuins act as 'double-edged swords'. Here, we provide an integrated overview of the different findings on the role of mammalian sirtuins in neurodegenerative and cardiometabolic disorders and attempt to dissect the reasons behind these different effects. Finally, we discuss how addressing these obstacles may provide a better understanding of the complex sirtuin biology and improve the likelihood of identifying effective and selective drug targets for a variety of human disorders.
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