Abstract
While ATP is recognized as an intracellular energy source for many biochemical reactions, it is now recognised it is also an important extracellular signalling molecule. ATP is involved in both physiological and pathological events in most cell types, and receptor subtypes have been cloned and characterised. An important goal of purinergic research today is to annotate the human genome with functional information regarding the role of genes for purinergic receptors, ectonucleotidases and transporters, in brain physiology and pathology. Insights into these roles have been gained also from studies of the various purinergic knockouts, and here we report on the generation of these purinergic receptor/ectonucleotidase-null mice. Recent X-ray structures of purinergic ligand-activated receptors provide promising templates to understand the molecular mechanism of receptor actions at the atomic level, and to deploy X-ray structures to be used for structure-based drug design. In the present work we also summarize recent findings about X-ray structures of ionotropic and metabotropic purinergic receptors and ectonucleotidases. A novel and prominent role as modulators of signal propagation in animal cells is played by microRNAs. By acting as genetic switches, they might become stringent regulators of the variety of cellular responses triggered by the dynamic interactions between purinergic receptors, nucleotides/nucleosides, transporters and ectonucleotidases. In this review we highlight data on the regulation of purinergic mechanisms by microRNAs. Finally, we would like to illustrate what information is still missing or needed for the acquisition of a more complete knowledge of purinergic signalling.
Keywords: Ectonucleotidases, extracellular adenosine, extracellular ATP, nervous system, purinergic signalling, purinergic receptors, Argonaute, Brain Derived Neurotrophic Factor, Central Nervous System, Tumor Necrosis Factor-alpha
CNS & Neurological Disorders - Drug Targets
Title:Purinergic Signalling: What is Missing and Needed Next? The Use of Transgenic Mice, Crystallographic Analysis and MicroRNA
Volume: 11 Issue: 6
Author(s): C. Volonte, C. Parisi and G. Burnstock
Affiliation:
Keywords: Ectonucleotidases, extracellular adenosine, extracellular ATP, nervous system, purinergic signalling, purinergic receptors, Argonaute, Brain Derived Neurotrophic Factor, Central Nervous System, Tumor Necrosis Factor-alpha
Abstract: While ATP is recognized as an intracellular energy source for many biochemical reactions, it is now recognised it is also an important extracellular signalling molecule. ATP is involved in both physiological and pathological events in most cell types, and receptor subtypes have been cloned and characterised. An important goal of purinergic research today is to annotate the human genome with functional information regarding the role of genes for purinergic receptors, ectonucleotidases and transporters, in brain physiology and pathology. Insights into these roles have been gained also from studies of the various purinergic knockouts, and here we report on the generation of these purinergic receptor/ectonucleotidase-null mice. Recent X-ray structures of purinergic ligand-activated receptors provide promising templates to understand the molecular mechanism of receptor actions at the atomic level, and to deploy X-ray structures to be used for structure-based drug design. In the present work we also summarize recent findings about X-ray structures of ionotropic and metabotropic purinergic receptors and ectonucleotidases. A novel and prominent role as modulators of signal propagation in animal cells is played by microRNAs. By acting as genetic switches, they might become stringent regulators of the variety of cellular responses triggered by the dynamic interactions between purinergic receptors, nucleotides/nucleosides, transporters and ectonucleotidases. In this review we highlight data on the regulation of purinergic mechanisms by microRNAs. Finally, we would like to illustrate what information is still missing or needed for the acquisition of a more complete knowledge of purinergic signalling.
Export Options
About this article
Cite this article as:
Volonte C., Parisi C. and Burnstock G., Purinergic Signalling: What is Missing and Needed Next? The Use of Transgenic Mice, Crystallographic Analysis and MicroRNA, CNS & Neurological Disorders - Drug Targets 2012; 11 (6) . https://dx.doi.org/10.2174/187152712803581146
DOI https://dx.doi.org/10.2174/187152712803581146 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
Related Articles
-
Molecular Genetics and Biomarkers of Polyglutamine Diseases
Current Molecular Medicine Antiepileptic Drug Interactions - Principles and Clinical Implications
Current Neuropharmacology Zebrafish as a Platform for Studies on Seizures and Epilepsy
Current Psychopharmacology VIP in Neurological Diseases: More Than A Neuropeptide
Endocrine, Metabolic & Immune Disorders - Drug Targets 2-Arylindoles: A Privileged Molecular Scaffold with Potent, Broad-Ranging Pharmacological Activity
Current Medicinal Chemistry Novel Insights into V-ATPase Functioning: Distinct Roles for its Accessory Subunits ATP6AP1/Ac45 and ATP6AP2/(pro) Renin Receptor
Current Protein & Peptide Science Recent Updates of N-Type Calcium Channel Blockers with Therapeutic Potential for Neuropathic Pain and Stroke
Current Topics in Medicinal Chemistry Ethanolamine: A Potential Promoiety with Additional Effects on the Brain
CNS & Neurological Disorders - Drug Targets MicroRNAs in CAG Trinucleotide Repeat Expansion Disorders: an Integrated Review of the Literature
CNS & Neurological Disorders - Drug Targets Davunetide: Peptide Therapeutic in Neurological Disorders
Current Medicinal Chemistry Defining Primary and Secondary Progenitor Disorders in the Brain: Proteomic Approaches for Analysis of Neural Progenitor Cells
Current Pharmaceutical Biotechnology Dietary Flavonoids Interaction with CREB-BDNF Pathway: An Unconventional Approach for Comprehensive Management of Epilepsy
Current Neuropharmacology Nanosized Drug Delivery Systems for Direct Nose to Brain Targeting: A Review
Recent Patents on Drug Delivery & Formulation To Analyze the Amelioration of Phenobarbital Induced Oxidative Stress by Erucin, as Indicated by Biochemical and Histological Alterations
Anti-Cancer Agents in Medicinal Chemistry The Role of mGlu Receptors in Hippocampal Plasticity Deficits in Neurological and Psychiatric Disorders: Implications for Allosteric Modulators as Novel Therapeutic Strategies
Current Neuropharmacology Insight Into the Emerging Role of Striatal Neurotransmitters in the Pathophysiology of Parkinson’s Disease and Huntington’s Disease: A Review
Current Neuropharmacology Emerging Use of Nanotechnology in the Treatment of Neurological Disorders
Current Pharmaceutical Design Inhibitors of Aldo-Keto Reductases AKR1C1-AKR1C4
Current Medicinal Chemistry Electroconvulsive Therapy in Child and Adolescent Psychiatry
Current Psychiatry Reviews Cannabis Associated “High” Cardiovascular Morbidity and Mortality: Marijuana Smoke Like Tobacco Smoke? A Déjà Vu/Déjà Vécu Story?
Mini-Reviews in Medicinal Chemistry