Current Drug Targets - Volume 14, Issue 6, 2013

The rising incidence of type 2 diabetes mellitus (T2DM) is a major public health problem in industrialized countries, and new therapeutic strategies to prevent T2DM are urgently needed worldwide. It is well known that calorie restriction (CR) can retard the aging process in organisms ranging from yeast to rodents and delay the onset of numerous age-related diseases, including diabetes. Molecules that mimic CR metabolically Read More

Nicotinamide adenine dinucleotide (NAD+) biosynthesis from nicotinamide is used by mammalian cells to replenish their NAD+ stores and to avoid unwanted nicotinamide accumulation. Pharmacological inhibition of nicotinamide phosphoribosyltransferase (NAMPT), the key enzyme in this biosynthetic pathway, almost invariably leads to intracellular NAD+ depletion and, when protracted, to ATP shortage and cell demise. Ca Read More

Age-related diseases pose as an enormous problem on aging populations of the world. Despite the fact that many advances have been made on understanding of the neurodegeneration, there is still no cure available for the agerelated brain disorders. Sirtuins are NAD-dependent protein deacetylases that were shown to have beneficial effects against age-related diseases. SIRT1 and SIRT2 have been studied mostly in ter Read More

Sirtuins are a family of NAD+-dependent protein deacetylases, which regulate cell survival and energy metabolism, inflammation and cancer. Recent studies have shown that sirtuin-1 (SIRT1) modulates Human Immunodeficiency Virus (HIV)-1 transcription. The HIV-1 Tat protein is a substrate for the deacetylase activity of SIRT1; SIRT1 recycles Tat to its unacetylated form, catalyzing a fundamental step to start new c Read More

Sir2-like proteins (Sirtuins) are a class of enzymes conserved throughout the kingdoms of life. In fact, from Archaea to Mammals, these (class III) NAD+-dependent deacetylases catalyse the removal of the acetyl moiety from a substrate protein. Sirtuins show a conserved central catalytic domain with two more variable amino- and carboxy-terminal flanking regions. Amino acid comparison of these central conserved cataly Read More

Sirtuins form a large homology family of enzymes found almost ubiquitously in living organisms and involved in numerous biological processes. The human genome encodes for seven paralog sirtuins, identified as SIRT1 – 7. In this review the major structural features of the sirtuin catalytic domain are illustrated and the relevant sources of biological information indicated. The multiple sequence alignment deduced from the Read More

Silent information regulator 2 (Sir2) proteins, or sirtuins, are a family of proteins which influence several physiological responses and have implications for treating diseases of ageing. In this context, we have presented a summarized view on the discovery of Sir2 family proteins, the enzymatic activities, the role of sirtuins in aging, lifespan and onset of age-related symptoms. In addition, we have described the roles of Read More

Tuberculosis (TB) is an infectious disease caused by the pathogen Mycobacterium tuberculosis (M. tuberculosis), killing about two million people worldwide each year. An increase in the prevalence of drug-resistant strains of M. tuberculosis in the past decades has renewed focus on the development of new drugs that can treat both drug-sensitive and resistant TB infections. M. tuberculosis evades the host immune syste Read More

The hypoxic microenvironment is a clinicopathological characteristic of many diseases, such as rheumatoid arthritis (RA). As a transcription factor activating the gene expression involved in processes such as cell metabolism and angiogenesis, hypoxia-inducible factor (HIF) has a central function in adaption to altered oxygen tension and even contributes to the progression of related diseases. In RA, HIF induces angiogenesis, cell Read More

Psoriasis is a multifactorial autoimmune skin disorder based on irregularities of the T- cell function. The abnormal keratinocyte hyper proliferation in psoriasis arises due to the activation of T-cells which produces rich amount of arachidonic acid leads to generation of various proinflammatory mediators like PGs, LTs, cytokines and adhesion molecules via MAPK/AP-1, EARK1/2 and protein kinase – C (PKCs) activation pathways. In Read More