Role Of Nicotinamide Adenine Dinucleotide Research Articles

The Role of NAD+ and NAD+-Boosting Therapies in Inflammatory Response by IL-13.

The essential role of nicotinamide adenine dinucleotide+ (NAD+) in redox reactions during oxidative respiration is well known, yet the coenzyme and regulator functions of NAD+ in diverse and important processes are still being discovered. Maintaining NAD+ levels through diet is essential for health. In fact, the United States requires supplementation of the NAD+ precursor niacin into the food chain for these reasons. A large body of research also indicates that elevating NAD+ levels is beneficial for numerous conditions, including cancer, cardiovascular health, inflammatory response, and longevity. Consequently, strategies have been created to elevate NAD+ levels through dietary supplementation with NAD+ precursor compounds. This paper explores current research regarding these therapeutic compounds. It then focuses on the NAD+ regulation of IL-13 signaling, which is a research area garnering little attention. IL-13 is a critical regulator of allergic response and is associated with Parkinson's disease and cancer. Evidence supporting the notion that increasing NAD+ levels might reduce IL-13 signal-induced inflammatory response is presented. The assessment is concluded with an examination of reports involving popular precursor compounds that boost NAD+ and their associations with IL-13 signaling in the context of offering a means for safely and effectively reducing inflammatory response by IL-13.

NMNATs expression inhibition mediated NAD+ deficiency plays a critical role in doxorubicin-induced hepatotoxicity in mice

Doxorubicin (DOX) is one of the most widely used antineoplastic drugs with known cardiotoxicity while other organ toxicity, such as hepatotoxicity is not well defined. This study was to explore the role of nicotinamide adenine dinucleotide (NAD+) in DOX-induced hepatotoxicity. DOX (20 mg/kg) induced acute liver injury and oxidative stress in C57BL/6 J mice at 48 h. Notably, the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and NAD(P)H dehydrogenase quinone 1 (NQO1) were downregulated. NAD+ deficiency was confirmed due to DOX exposure. Mechanistically, the downregulation of nicotinamide mononucleotide adenylyl transferase 1 (NMNAT1), NMNAT2 and NMNAT3, while no alteration of nicotinamide phosphoribosyl transferase was proved. As a consequence of NAD+ deficiency, the expression of poly-ADP-ribose polymerase1 (PARP1), CD38 and Sirtuin1 (SIRT1) were reduced. Furthermore, supplementation of NAD+ (200 mg/kg/day) or its precursor nicotinamide mononucleotide (NMN) (500 mg/kg/day) alleviated liver injury, attenuated oxidative stress, and elevated the downregulation of Nrf2 and NQO1. More importantly, compromised expression of NMNAT1–3, PARP1, CD38 and SIRT1 were improved by NAD+ and NMN. In conclusion, NAD+ deficiency due to NMNATs expression inhibition may attribute to the pathogenesis of DOX-induced hepatotoxicity, thus providing new insights for mitigating DOX side effects.

Deletion of enzymes for de novo NAD+ biosynthesis accelerated ovarian aging.

Recent advances highlight the pivotal role of nicotinamide adenine dinucleotide (NAD+ ) in ovarian aging. However, the roles of de novo NAD+ biosynthesis on ovarian aging are still unknown. Here, we found that genetic ablation of Ido1 (indoleamine-2,3-dioxygenase 1) or Qprt (Quinolinate phosphoribosyl transferase), two critical genes in de novo NAD+ biosynthesis, resulted in decreased ovarian NAD+ levels in middle-aged mice, leading to subfertility, irregular estrous cycles, reduced ovarian reserve, and accelerated aging. Moreover, we observed impaired oocyte quality, characterized by increased reactive oxygen species and spindle anomalies, which ultimately led to reduced fertilization ability and impaired early embryonic development. A transcriptomic analysis of ovaries in both mutant and wild-type mice revealed alterations in gene expression related to mitochondrial metabolism. Our findings were further supported by the observation of impaired mitochondrial distribution and decreased mitochondrial membrane potential in the oocytes of knockout mice. Supplementation with nicotinamide riboside (NR), an NAD+ booster, in mutant mice increased ovarian reserve and improved oocyte quality. Our study highlights the importance of the NAD+ de novo pathway in middle-aged female fertility.

#3828 KINETICS OF THE DE NOVO NAD/NADH PATHWAY FROM AKI TO CKD

Abstract Background and Aims Mitochondrial dysfunction and energy metabolism deficiency are part of the acute kidney injury (AKI) pathophysiology. In particular, recent studies highlighted the role of nicotinamide adenine dinucleotide (NAD) production in the pathogenesis of AKI. NAD is an electron carrier for mitochondria and a cofactor for cytoplasmic redox reactions. Its production is decreased during AKI following a decreased of the expression of PGC1α (Peroxisome proliferator activated receptor gamma co-activator-1-α). PGC1α inactivation worsened and its overexpression prevented renal injury in a mouse model of renal ischemia. It was also shown that the consequences of PGC1α decreased expression included the alteration of the de novo NAD+ synthesis pathway. This was due to a reduction in the expression of the Quinolinate PhosphoRibosylTransferase (QPRT), which led to an accumulation of quinolinate. Consequently, the quinolinate/tryptophane (uQ/T) ratio increased in the urine. The modulation of this de novo has been studied mainly in the acute phase immediately following the injury. However its evolution with degree of severity and during the transition from AKI to CKD has not been described yet. In order to answer these questions, we designed the following studies: (1) A “severity” study in which we provoked ischemic AKI of increasing intensity in mice and quantified kidney PGC1alpha and QPRT mRNA expression. (2) An “AKI to CKD” study in which we followed kidney PGC1alpha and QPRT mRNA expression and uQ/T. Method Renal ischemia-reperfusion was performed in C57Bl6/J male mice using the new vascular occluder we recently developed (RIRI clamp), after nephrectomy of the contralateral kidney. For the ‘severity’ study, a 5–30 minutes ischemia was performed. Renal function (measurement of plasma creatinine and urea) and structure (Periodic Acid Schiff staining) were assessed 24h after ischemia. For the ‘AKI to CKD’ study, renal ischemia was performed during 10 minutes. Mice were sacrificed 1, 2, 3, 6 and 28 days after ischemia. For both studies, PGC1α and QPRT mRNA expression was quantified by qPCR in the kidneys. Urinary Q/T was determined by mass spectrometry. Results PGC1α and QPRT mRNA expression is inversely corrected to the AKI severity We induced AKI in mice by unilateral ischemia reperfusion injury of increasing time to induce several degrees of AKI severity. The measurement of plasma urea and creatinine concentration confirmed that the severity increased with the duration of ischemia. PGC1α and QPRT mRNA expression decreased progressively with ischemia severity until reaching a plateau at 15 minutes of ischemia for PGC1α (Fig. 1A), like plasma creatinine and urea, whereas QPRT (Fig. 1B) decreased is linear until 30 min of ischemia. PGC1α mRNA decrease is also inversely correlated to kidney dysfunction (p<0.001) (Figue 1C). PGC1α and QPRT expression recovery after AKI A 10-minute ischemia led to the development of Chronic Kidney Disease (CKD), as evidenced by an incomplete recuperation of the kidney function at 28 days. QPRT and PGC1α mRNA expression showed a progressive but incomplete recuperation during the transition from AKI to CKD compared to sham mice (Fig. 1D, E). uQ/T increases after ischemia and is restored during transition from AKI to CKD (Fig. 1F). Conclusion In addition to confirming the decrease of PGCα and QPRT mRNA expression during AKI, we show that it is correlated to the severity of the ischemic AKI. Furthermore, we describe the recovery during renal repair and transition to CKD.

Perspective: Can early embryonic losses be reduced in lactating dairy cows?

Perspective: Can early embryonic losses be reduced in lactating dairy cows?

Importance of NAD+ Anabolism in Metabolic, Cardiovascular and Neurodegenerative Disorders.

The role of nicotinamide adenine dinucleotide (NAD+) in ageing has emerged as a critical factor in understanding links to a wide range of chronic diseases. Depletion of NAD+, a central redox cofactor and substrate of numerous metabolic enzymes, has been detected in many major age-related diseases. However, the mechanisms behind age-associated NAD+ decline remains poorly understood. Despite limited conclusive evidence, supplements aimed at increasing NAD+ levels are becoming increasingly popular. This review provides renewed insights regarding the clinical utility and benefits of NAD+ precursors, namely nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), in attenuating NAD+ decline and phenotypic characterization of age-related disorders, including metabolic, cardiovascular and neurodegenerative diseases. While it is anticipated that NAD+ precursors can play beneficial protective roles in several conditions, they vary in their ability to promote NAD+ anabolism with differing adverse effects. Careful evaluation of the role of NAD+, whether friend or foe in ageing, should be considered.

MicroRNA-26b Reduces Cell Viability by Inhibition of Nicotinamide Phosphoribosyltransferase in Breast Cancer Cells

Breast cancer (BC) is one of the most common causes of cancer in women worldwide and it is found to be associated with an increased level of Nicotinamide phosphoribosyltransferase (NAMPT), which plays an important role in nicotinamide adenine dinucleotide (NAD) pathway, both in blood and tumor tissues. This enzyme is also essential for the growth and survival of cancer cells. The short noncoding RNA microRNAs miR-26b is an important gene regulator and a tumor suppressor in different human cancers, including BC. In this study, bioinformatics analysis was evaluated to find the miRNAs targeting NAMPT 3' untranslated regions (3' UTRs), which was confirmed by luciferase assay. Next, we evaluate NAMPT and microRNA-26b (miR-26b) expression by using polymerase chain reaction (PCR) in BC. miR-26b effect on cell viability was also evaluated by Cell Counting Kit-8 (CCK-8). Following transfection with miR-613 mimic, the expression of miR-613 was elevated in the BC cells leading to inhibition of NAMPT expression at both mRNA and protein level as measured by real-time PCR and western blotting. Our result identified a significant tumor suppressor role of miR-26b on NAMPT, NAD concentration, and cell viability in BC. Overall, based on our finding, miR-26b mimic transfection could elevate miR-26b levels in BC cells via downregulating the NAMPT expression, NAD expression levels, and cell growth, whereas miR-26b inhibitor had the opposite function. In conclusion, miR-26b can become a promising target for BC treatment through targeting NAMPT and inhibiting the NAD production.

The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae.

Molecular causes of aging and longevity interventions have witnessed an upsurge in the last decade. The resurgent interests in the application of small molecules as potential geroprotectors and/or pharmacogenomics point to nicotinamide adenine dinucleotide (NAD) and its precursors, nicotinamide riboside, nicotinamide mononucleotide, nicotinamide, and nicotinic acid as potentially intriguing molecules. Upon supplementation, these compounds have shown to ameliorate aging related conditions and possibly prevent death in model organisms. Besides being a molecule essential in all living cells, our understanding of the mechanism of NAD metabolism and its regulation remain incomplete owing to its omnipresent nature. Here we discuss recent advances and techniques in the study of chronological lifespan (CLS) and replicative lifespan (RLS) in the model unicellular organism Saccharomyces cerevisiae. We then follow with the mechanism and biology of NAD precursors and their roles in aging and longevity. Finally, we review potential biotechnological applications through engineering of microbial lifespan, and laid perspective on the promising candidature of alternative redox compounds for extending lifespan.

Integrated In Silico Studies on the Role of Nicotinamide Adenine Dinucleotide (NADH) Binding in Activating C-Terminal Binding Protein 2 (CtBP2)

Abstract The C-terminal binding protein 2 (CtBP2) plays a role in apoptosis and embryogenesis. Genetic knockout studies have been demonstrated to cause severe developmental defects and embryonic lethality. CtBP2 has three key domains and dimerizes for a significant role by binding with nicotinamide adenine dinucleotide (NADH). However, the molecular mechanism of CtBP2 dimerization and the effect of NADH binding are unknown. In this study, we performed molecular dynamics (MD) and docking simulation to reveal the mechanism of C-terminal binding protein 2 (CtBP2) dimerization and the effect of NADH binding on the dimer formation. Our MD simulation results detected seven salt bridges that are important for CtBP2 dimerization. And docking simulation demonstrated that the holo-monomer gave a higher probability of correct docking pose than the apo-monomer. Moreover, in docking simulation using a PXDLS model peptide, that holo form gave more docking poses than that apo form. These results suggested that the holo form has a structure that facilitates the formation of dimers and the binding of PXDLS peptides.

Description of Visfatin Adipokine and its Roles on Inflammation and Coronary Heart Disease

Coronary heart disease (CHD) is a generic designation for a group of related syndromes resulting from myocardial ischemia – an imbalance between cardiac blood supply (perfusion) and myocardial oxygen demand. Visfatin (VF) is a recently discovered adipokine with different functions, Visfatin is mainly found in visceral adipose tissue and mimics insulin in lowering plasma glucose levels and, Visfatin emerges as a player in the development and progression of atherosclerotic lesions by directly promoting smooth muscle cell proliferation, Aberrant angiogenesis is now considered a feature of the atherogenic process in both coronary and carotid diseases. This adipokine was previously known as a pre-B-cell colony-enhancing factor (PBEF) or Nicotinamide phosphoribosyltransferase (NAmPRTase or Nampt) an enzyme that in humans is encoded by the NAMPT gene and demonstrated to be an intracellular protein with a key enzyme role in nicotinamide adenine dinucleotide (NAD)

The NADase enzyme CD38: an emerging pharmacological target for systemic sclerosis, systemic lupus erythematosus and rheumatoid arthritis.

Here we review recent literature on the emerging role of nicotinamide adenine dinucleotide (NAD) metabolism and its dysfunction via the enzyme CD38 in the pathogenesis of rheumatologic diseases. We evaluate the potential of targeting CD38 to ameliorate NAD-related metabolic imbalance and tissue dysfunction in the treatment of systemic sclerosis (SSc), systemic lupus erythematous (SLE), and rheumatoid arthritis (RA). In this review, we will discuss emerging basic, preclinical, and human data that point to the novel role of CD38 in dysregulated NAD-homeostasis in SSc, SLE, and RA. In particular, recent studies implicate increased activity of CD38, one of the main enzymes in NAD catabolism, in the pathogenesis of persistent systemic fibrosis in SSc, and increased susceptibility of SLE patients to infections. We will also discuss recent studies that demonstrate that a cytotoxic CD38 antibody can promote clearance of plasma cells involved in the generation of RA antibodies. Recent studies identify potential therapeutic approaches for boosting NAD to treat rheumatologic diseases including SSc, RA, and SLE, with particular attention to inhibition of CD38 enzymatic activity as a target. Key future directions in the field include the determination of the cell-type specificity and role of CD38 enzymatic activity versus CD38 structural roles in human diseases, as well as the indicators and potential side effects of CD38-targeted treatments.

SIRT3-Dependent Mitochondrial Dynamics Remodeling Contributes to Oxidative Stress-Induced Melanocyte Degeneration in Vitiligo.

Mitochondrial dysregulation has been implicated in oxidative stress-induced melanocyte destruction in vitiligo. However, the molecular mechanism underlying this process is merely investigated. Given the prominent role of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase Sirtuin3 (SIRT3) in sustaining mitochondrial dynamics and homeostasis and that SIRT3 expression and activity can be influenced by oxidative stress-related signaling, we wondered whether SIRT3 could play an important role in vitiligo melanocyte degeneration by regulating mitochondrial dynamics.Methods: We initially testified SIRT3 expression and activity in normal and vitiligo melanocytes via PCR, immunoblotting and immunofluorescence assays. Then, cell apoptosis, mitochondrial function and mitochondrial dynamics after SIRT3 intervention were analyzed by flow cytometry, immunoblotting, confocal laser microscopy, transmission electron microscopy and oxphos activity assays. Chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP), immunoblotting and immunofluorescence assays were performed to clarify the upstream regulatory mechanism of SIRT3. Finally, the effect of honokiol on protecting melanocytes and the underlying mechanism were investigated via flow cytometry and immunoblotting analysis.Results: We first found that the expression and the activity of SIRT3 were significantly impaired in vitiligo melanocytes both in vitro and in vivo. Then, SIRT3 deficiency led to more melanocyte apoptosis by inducing severe mitochondrial dysfunction and cytochrome c release to cytoplasm, with Optic atrophy 1 (OPA1)-mediated mitochondrial dynamics remodeling involved in. Moreover, potentiated carbonylation and dampened peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) activation accounted for SIRT3 dysregulation in vitiligo melanocytes. Finally, we proved that honokiol could prevent melanocyte apoptosis under oxidative stress by activating SIRT3-OPA1 axis.Conclusions: Overall, we demonstrate that SIRT3-dependent mitochondrial dynamics remodeling contributes to oxidative stress-induced melanocyte degeneration in vitiligo, and honokiol is promising in preventing oxidative stress-induced vitiligo melanocyte apoptosis.

The Role of Nicotinamide Adenine Dinucleotide in the Pathogenesis of Rheumatoid Arthritis: Potential Implications for Treatment

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory, autoimmune disease characterised by small joint swelling, deformity, and dysfunction. Its exact aetiology is unclear. Current treatment approaches do not control harmful autoimmune attacks or prevent irreversible damage without considerable side effects. Nicotinamide adenine dinucleotide (NAD+), an important hydrogen carrier in mitochondrial respiration and oxidative phosphorylation, is the major determinant of redox state in the cell. NAD+ metabolites act as degradation substrates for a wide range of enzymes, such as sirtuins, poly-ADP-ribose polymerases, ADP-ribosyltransferases, and CD38. The roles of NAD+ have expanded beyond its role as a coenzyme, linking cellular metabolism to inflammation signalling and immune response. The aim of this review is to illustrate the role of NAD+-related enzymes in the pathogenesis of RA and highlight the potential therapeutic role of NAD+ in RA.

Role of Nicotinamide Adenine Dinucleotide and Related Precursors as Therapeutic Targets for Age-Related Degenerative Diseases: Rationale, Biochemistry, Pharmacokinetics, and Outcomes.

Significance: Nicotinamide adenine dinucleotide (NAD+) is an essential pyridine nucleotide that serves as an essential cofactor and substrate for a number of critical cellular processes involved in oxidative phosphorylation and ATP production, DNA repair, epigenetically modulated gene expression, intracellular calcium signaling, and immunological functions. NAD+ depletion may occur in response to either excessive DNA damage due to free radical or ultraviolet attack, resulting in significant poly(ADP-ribose) polymerase (PARP) activation and a high turnover and subsequent depletion of NAD+, and/or chronic immune activation and inflammatory cytokine production resulting in accelerated CD38 activity and decline in NAD+ levels. Recent studies have shown that enhancing NAD+ levels can profoundly reduce oxidative cell damage in catabolic tissue, including the brain. Therefore, promotion of intracellular NAD+ anabolism represents a promising therapeutic strategy for age-associated degenerative diseases in general, and is essential to the effective realization of multiple benefits of healthy sirtuin activity. The kynurenine pathway represents the de novo NAD+ synthesis pathway in mammalian cells. NAD+ can also be produced by the NAD+ salvage pathway. Recent Advances: In this review, we describe and discuss recent insights regarding the efficacy and benefits of the NAD+ precursors, nicotinamide (NAM), nicotinic acid (NA), nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN), in attenuating NAD+ decline in degenerative disease states and physiological aging. Critical Issues: Results obtained in recent years have shown that NAD+ precursors can play important protective roles in several diseases. However, in some cases, these precursors may vary in their ability to enhance NAD+ synthesis via their location in the NAD+ anabolic pathway. Increased synthesis of NAD+ promotes protective cell responses, further demonstrating that NAD+ is a regulatory molecule associated with several biochemical pathways. Future Directions: In the next few years, the refinement of personalized therapy for the use of NAD+ precursors and improved detection methodologies allowing the administration of specific NAD+ precursors in the context of patients' NAD+ levels will lead to a better understanding of the therapeutic role of NAD+ precursors in human diseases.

Mast cells regulate CD4+ T-cell differentiation in the absence of antigen presentation

Given their unique capacity for antigen uptake, processing, and presentation, antigen-presenting cells (APCs) are critical for initiating and regulating innate and adaptive immune responses. We have previously shown the role of nicotinamide adenine dinucleotide (NAD+) in T-cell differentiation independently of the cytokine milieu, whereas the precise mechanisms remained unknown. The objective of this study is to further dissect the mechanism of actions of NAD+ and determine the effect of APCs on NAD+-mediated T-cell activation. Isolated dendritic cells and bone marrow-derived mast cells (MCs) were used to characterize the mechanisms of action of NAD+ on CD4+ T-cell fate invitro. Furthermore, NAD+-mediated CD4+ T-cell differentiation was investigated invivo by using wild-type C57BL/6, MC-/-, MHC class II-/-, Wiskott-Aldrich syndrome protein (WASP)-/-, 5C.C7 recombination-activating gene 2 (Rag2)-/-, and CD11b-DTR transgenic mice. Finally, we tested the physiologic effect of NAD+ on the systemic immune response in the context of Listeria monocytogenes infection. Our invivo and invitro findings indicate that after NAD+ administration, MCs exclusively promote CD4+ T-cell differentiation, both in the absence of antigen and independently of major APCs. Moreover, we found that MCs mediated CD4+ T-cell differentiation independently of MHC II and T-cell receptor signaling machinery. More importantly, although treatment with NAD+ resulted in decreased MHC II expression on CD11c+ cells, MC-mediated CD4+ T-cell differentiation rendered mice resistant to administration of lethal doses of L monocytogenes. Collectively, our study unravels a novel cellular and molecular pathway that regulates innate and adaptive immunity through MCs exclusively and underscores the therapeutic potential of NAD+ in the context of primary immunodeficiencies and antimicrobial resistance.

Regeneration of NAD keeps mouse muscles young

Aging Evidence for a critical role of nicotinamide adenine dinucleotide (NAD) metabolism in aging is accumulating. Frederick et al. studied mice with muscle-specific depletion of nicotinamide phosphoribosyltransferase (Nampt), an enzyme needed to restore concentrations of NAD in working muscle.

Nicotinamide: a vitamin able to shift macrophage differentiation toward macrophages with restricted inflammatory features.

The differentiation of human monocytes into macrophages is influenced by environmental signals. Here we asked in how far nicotinamide (NAM), a vitamin B3 derivative known to play a major role in nicotinamide adenine dinucleotide (NAD)-mediated signaling events, is able to modulate monocyte differentiation into macrophages developed in the presence of granulocyte macrophage colony-stimulating factor (GM-MØ) or macrophage colony-stimulating factor (M-MØ). We found that GM-MØ undergo biochemical, morphological and functional modifications in response to NAM, whereas M-MØ were hardly affected. GM-MØ exposed to NAM acquired an M-MØ-like structure while the LPS-induced production of pro-inflammatory cytokines and COX-derived eicosanoids were down-regulated. In contrast, NAM had no effect on the production of IL-10 or the cytochrome P450-derived eicosanoids. Administration of NAM enhanced intracellular NAD concentrations; however, it did not prevent the LPS-mediated drain on NAD pools. In search of intracellular molecular targets of NAM known to be involved in LPS-induced cytokine and eicosanoid synthesis, we found NF-κB activity to be diminished. In conclusion, our data show that vitamin B3, when present during the differentiation of monocytes into GM-MØ, interferes with biochemical pathways resulting in strongly reduced pro-inflammatory features.

Complex role of nicotinamide adenine dinucleotide in the regulation of programmed cell death pathways

Over the past few years, a growing body of experimental observations has led to the identification of novel and alternative programs of regulated cell death. Recently, autophagic cell death and controlled forms of necrosis have emerged as major alternatives to apoptosis, the best characterized form of regulated cell demise. These recently identified, caspase-independent, forms of cell death appear to play a role in the response to several forms of stress, and their importance in different pathological conditions such as ischemia, infection and inflammation has been recognized. The functional link between cell metabolism and survival has also been the matter of recent studies. Nicotinamide adenine dinucleotide (NAD+) has gained particular interest due to its role in cell energetics, and as a substrate for several families of enzymes, comprising poly ADP-ribose polymerases (PARPs) and sirtuins, involved in numerous biological functions including cell survival and death. The recently uncovered diversity of cell death programs has led us to reevaluate the role of this important metabolite as a universal pro-survival factor, and to discuss the potential benefits and limitations of pharmacological approaches targeting NAD+ metabolism.

NAD Metabolism and Functions: A Common Therapeutic Target for Neoplastic, Metabolic and Neurodegenerative Diseases

In recent years the study of nicotinamide adenine dinucleotide (NAD) biochemistry has been the focus of attention for many researchers. Although the role of NAD in cellular metabolism and in redox reactions had been recognized for over a century, it was also during these recent studies that the precise identification of all NAD biosynthetic routes was achieved and that the variety of NAD controlled cellular processes began to emerge. Being vital not only for energy transduction, but also for intracellular signaling pathways, this pyridine nucleotide can be considered the most important link between energetic and regulatory processes. The control of such important events suggested NAD as a possible therapeutic target for the control of different pathological states, including metabolic disorders and neoplastic transformation. This review briefly summarizes the recent advances achieved in this field.

Sirtuin mediated neuroprotection and its association with autophagy and apoptosis: Studies employing transgenic C. elegans model

Background Sirtuins, NAD+-dependent protein deacetylases, are well known for their role in longevity. Aging is the major known risk factor for the onset of Parkinson’s disease (PD). In our previous studies, SIRT1 induction by calorie restriction (CR) diet regimen has been shown to protect against dopaminergic neurodegeneration via sir-2.1 mediated pathway. Taking the studies forward, we endeavoured to understand the role of nicotinamide adenine dinucleotide activated protein deacetylase Sir2p/Sirt1 in calorie restriction mediated prevention of Parkinsonism employing transgenic Caenorhabditis elegans expressing human alpha synuclein.