A review of Sirt1 and Sirt1 modulators in cardiovascular and metabolic diseases.
Sirt1 (member of the sirtuin family) is a nicotinamide adenosine dinucleotide (NAD)-dependent deacetylase that removes acetyl groups from various proteins. A wide variety of proteins are Sirt1 substrates; the list includes many transcription factors and cofactors. Deacetylation of these factors may lead to activation or inactivation of the factor, thus impacting downstream gene expression. In addition to direct deacetylation, Sirt1 can modulate protein activity by other mechanisms. Although initial research focused on sirtuin's role in life span extension especially in lower organisms more recent studies show that Sirt1 activity can impact a wide array of proteins implicated in cardiovascular (CV) and metabolic diseases. Several patents have been published in the last 5 years describing the application of sirtuin compounds in the treatment of metabolic diseases. This review will focus on those Sirt1-modifiable proteins that have an impact on CV and metabolic diseases. Pharmacological agents that activate Sirt1 and thus impact the disease process will also be reviewed.
Pillarisetti
Sivaram
S
Reddy US Therapeutics, Inc., Dr Reddy Laboratories, Norcross, GA 30071, USA. ram@reddyus.com
D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology*; D004268:DNA-Binding Proteins / Q000502:physiology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D000071518:Liver X Receptors; D024821:Metabolic Syndrome / Q000209:etiology*; D016328:NF-kappa B / Q000502:physiology; D057093:Orphan Nuclear Receptors; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D056564:Sirtuin 1; D037761:Sirtuins / Q000187:drug effects / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; D000071518:Liver X Receptors; D016328:NF-kappa B; D057093:Orphan Nuclear Receptors; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins