Sirtuin deacetylases regulate diverse cellular pathways and influence disease processes. Our previous studies identified the brain-enriched sirtuin-2 (SIRT2) deacetylase as a potential drug target to counteract neurodegeneration. In the present study, we characterize SIRT2 inhibition activity of the brain-permeable compound AK7 and examine the efficacy of this small molecule in models of Parkin...

Sirtuins are an ancient family of NAD(+)-dependent deacylases connected with the regulation of fundamental cellular processes including metabolic homeostasis and genome integrity. We show the existence of a hitherto unrecognized class of sirtuins, found predominantly in microbial pathogens. In contrast to earlier described classes, these sirtuins exhibit robust protein ADP-ribosylation activity...

Posttranslational regulation of protein function by acetylation is present throughout nature. Regulation of protein function by Sir2 protein (sirtuin) deacetylases is conserved in all domains of life. In the prokaryote Salmonella enterica, the metabolic enzyme acetyl-coenzyme A synthetase (Acs) is regulated by a Sir2-dependent protein acetylation/deacetylation system (SDPADS). The recent identi...

Adult onset neuronal lipofuscinosis (ANCL) is a human neurodegenerative disorder characterized by progressive neuronal dysfunction and premature death. Recently, the mutations that cause ANCL were mapped to the DNAJC5 gene, which encodes cysteine string protein alpha. We show here that mutating dnj-14, the Caenorhabditis elegans orthologue of DNAJC5, results in shortened lifespan and a small im...

Sirtuins such as SIRT1 are conserved protein NAD(+)-dependent deacylases and thus their function is intrinsically linked to cellular metabolism. Over the past two decades, accumulating evidence has indicated that sirtuins are not only important energy status sensors but also protect cells against metabolic stresses. Sirtuins regulate the aging process and are themselves regulated by diet and en...

Sirtuin 1 ablation in endothelial cells is associated with impaired angiogenesis and 1 diastolic dysfunction 2 3 4 Julien MAIZEL1,3, Sandhya XAVIER3, Jun CHEN3, Chi Hua Sarah LIN3, Radovan VASKO1,2, 5 Michael S GOLIGORSKY3 6 7 1Medical Intensive Care Unit, Department of Nephrology and INSERM U-1088, University of 8 Picardie, Amiens, France, 2Department of Nephrology and Rheumatology, University...

Sirtuin 7 (SIRT7) is a NAD+-dependent deacetylase in the sirtuin family. In a previous study, human bone marrow mesenchymal stem cells (hBMSCs) with reduced SIRT7 activity were developed to evaluate the effect of SIRT7 on osteogenesis. SIRT7 knockdown significantly enhanced osteoblast-specific gene expression, alkaline phosphatase activity, and mineral deposition in vitro. Additionally, SIRT7 k...

OBJECTIVE Sirtuins (SIRTs) play a prominent role in metabolism, apoptosis, aging, inflammation, and epigenetics. Inflammation, apoptosis, and epigenetics are pathogenic issues in rheumatoid arthritis (RA). This study aimed to evaluate SIRT2 and SIRT3 mRNA expressions in patients with RA. MATERIAL AND METHODS Fifty-four patients with RA and 26 healthy controls were enrolled. Disease activity w...

Recent studies in mice have identified single molecules that can delay multiple diseases of aging and extend lifespan. In theory, such molecules could prevent dozens of diseases simultaneously, potentially extending healthy years of life. In this review, we discuss recent advances, controversies, opportunities, and challenges surrounding the development of SIRT1 activators, molecules with the p...

We have carried out a cell-based screen aimed at discovering small molecules that activate p53 and have the potential to decrease tumor growth. Here, we describe one of our hit compounds, tenovin-1, along with a more water-soluble analog, tenovin-6. Via a yeast genetic screen, biochemical assays, and target validation studies in mammalian cells, we show that tenovins act through inhibition of t...