Abstract
NAD plays a major role in all cells as substrate for signal transduction and as cofactor in metabolic redox reactions. Since NAD-dependent signaling involves degradation of the nucleotide, continuous restoration of cellular NAD pools is essential. Moreover, NAD-dependent signaling reactions, which include ADP-ribosylation, protein deacetylation by sirtuins and calcium messenger synthesis, are regulated by NAD availability. Consequently, perturbations of NAD supply can have severe consequences and, in fact, have been associated with major human diseases such as age- and dietinduced disorders, neurodegenerative diseases and cancer. Given the increasing awareness of the biological roles of NAD, the routes, molecular mechanisms and regulation of NAD biosynthesis have been the subject of intense research over the last decade. Impressive progress has been made regarding the molecular identification, functional and structural characterization as well as regulation of the human NAD biosynthetic enzymes. Exciting therapeutic concepts have emerged, which aim at modulation of NAD availability by interfering with the biosynthetic network to prevent, reduce or reverse pathological conditions. Since there are several entry points into NAD synthesis, including the known vitamin B3 precursors nicotinamide and nicotinic acid, targeted nutritional supplementation is likely to have beneficial effects in various diseases. On the other hand, inhibition of NAD synthesis promotes cell death and has emerged as a therapeutic concept for cancer treatment.
Keywords: Cancer, compartmentation, metabolism, niacin, signaling, sirtuins, vitamin B3.
Current Topics in Medicinal Chemistry
Title:NAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects
Volume: 13 Issue: 23
Author(s): Christian Dölle, Renate Hvidsten Skoge, Magali R. VanLinden and Mathias Ziegler
Affiliation:
Keywords: Cancer, compartmentation, metabolism, niacin, signaling, sirtuins, vitamin B3.
Abstract: NAD plays a major role in all cells as substrate for signal transduction and as cofactor in metabolic redox reactions. Since NAD-dependent signaling involves degradation of the nucleotide, continuous restoration of cellular NAD pools is essential. Moreover, NAD-dependent signaling reactions, which include ADP-ribosylation, protein deacetylation by sirtuins and calcium messenger synthesis, are regulated by NAD availability. Consequently, perturbations of NAD supply can have severe consequences and, in fact, have been associated with major human diseases such as age- and dietinduced disorders, neurodegenerative diseases and cancer. Given the increasing awareness of the biological roles of NAD, the routes, molecular mechanisms and regulation of NAD biosynthesis have been the subject of intense research over the last decade. Impressive progress has been made regarding the molecular identification, functional and structural characterization as well as regulation of the human NAD biosynthetic enzymes. Exciting therapeutic concepts have emerged, which aim at modulation of NAD availability by interfering with the biosynthetic network to prevent, reduce or reverse pathological conditions. Since there are several entry points into NAD synthesis, including the known vitamin B3 precursors nicotinamide and nicotinic acid, targeted nutritional supplementation is likely to have beneficial effects in various diseases. On the other hand, inhibition of NAD synthesis promotes cell death and has emerged as a therapeutic concept for cancer treatment.
Export Options
About this article
Cite this article as:
Dölle Christian, Skoge Hvidsten Renate, VanLinden R. Magali and Ziegler Mathias, NAD Biosynthesis in Humans - Enzymes, Metabolites and Therapeutic Aspects, Current Topics in Medicinal Chemistry 2013; 13 (23) . https://dx.doi.org/10.2174/15680266113136660206
DOI https://dx.doi.org/10.2174/15680266113136660206 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Anticancer, Antioxidant and Cytotoxic Potential of Thymol <i>in vitro</i> Brain Tumor Cell Model
Central Nervous System Agents in Medicinal Chemistry Combined <i>Curcuma longa</i> and <i>Cratoxylum formosum</i> Extracts Possess Anti-liver Cancer and Anti-HBV Activities in HepG2.2.15
Current Traditional Medicine Mitochondrial Superoxide Dismutase: A Promising Target for New Anticancer Therapies
Current Medicinal Chemistry Neuropharmacological Aspects of Crocus sativus L.: A Review of Preclinical Studies and Ongoing Clinical Research
CNS & Neurological Disorders - Drug Targets miRNAs in Cancer Prevention and Treatment and as Molecular Targets for Natural Product Anticancer Agents
Current Cancer Drug Targets Mechanisms of ERK1/2 Regulation by Seven-Transmembrane-Domain Receptors
Current Pharmaceutical Design Antioxidant and ‘Natural Protective’ Properties of Kiwifruit
Current Topics in Medicinal Chemistry Regulation of Apoptosis and Cell Survival by Resveratrol
Mini-Reviews in Organic Chemistry Dietary Fat and Hypertension: A Novel Approach Through the Proteolytic Regulatory Enzymes of the Renin-Angiotensin-System
Cardiovascular & Hematological Agents in Medicinal Chemistry Natural Compounds and Drug Discovery: Can Cnidarian Venom Play a Role?
Central Nervous System Agents in Medicinal Chemistry NPY and NPY Receptors in Vascular Remodeling
Current Topics in Medicinal Chemistry Insights into a Critical Role of the FOXO3a-FOXM1 Axis in DNA Damage Response and Genotoxic Drug Resistance
Current Drug Targets Metabolomics: A Revolution for Novel Cancer Marker Identification
Combinatorial Chemistry & High Throughput Screening Trends in Utilization of the Pharmacological Potential of Chalcones
Current Clinical Pharmacology Role of Alterations in the Apoptotic Machinery in Sensitivity of Cancer Cells to Treatment
Current Pharmaceutical Design A Medicinal Chemist’s Perspective Towards Structure Activity Relationship of Heterocycle Based Anticancer Agents
Current Topics in Medicinal Chemistry Mitochondrial Biogenesis in Health and Disease. Molecular and Therapeutic Approaches
Current Pharmaceutical Design Development and Clinical Application of Peptide-Based Radiopharmaceuticals
Current Pharmaceutical Design Genetic Predisposition to Neonatal Tumors
Current Pediatric Reviews Posttranslational Modifications of Tau - Role in Human Tauopathies and Modeling in Transgenic Animals
Current Drug Targets