This volume explores the quickly evolving field of Purinergic signaling, and examines how receptors for ATP and other nucleotides, and receptors for adenosine, act in neuronal transmission, control of synaptic activity, proliferation, differentiation and cell death regulation in the CNS. This book focuses on the participation of purinergic receptors and ectonucleotidases, degrading ATP into adenosine, in embryonic and adult neurogenesis in vitro and in vivo as well as in synaptic transmission and pathophysiology. Further, the chapters discuss varying brain diseases, including Parkinson’s, and Alzheimer’s disease, autism, mood disorders and epilepsy, as well as brain tumors, in the context of purinergic signaling and its clinical aspects. The development of purinergic receptor agonists is also an important issue of this book. This book provides a critical review of the current state of science and will be useful for both scientists and students who are or would like to get involved in this area. Furthermore, this book addresses neuroscientists, physician and professionals from the industry, who would like to update themselves in this exciting and rapidly growing field of neuroscience.
Author(s): Henning Ulrich, Peter Illes, Talita Glaser
Publisher: Springer
Year: 2023
Language: English
Pages: 380
City: Cham
Foreword
Preface
Contents
Chapter 1: Purinergic Signaling: An Overview
Discovery of the Purinergic System
Nomenclature and Components
Purinergic Signaling Perspectives
References
Chapter 2: Adenosine A2A Receptor-Containing Heteromers and Neuroprotection
Introduction
Adenosine and Neuroprotection
Heteromers of A2AR with Class C Metabotropic Glutamate Receptors
Heteromers of A2AR with Other Adenosine Receptor Subtypes
Heteromers of A2AR with Other Class A GPCRs
A2AR-Containing Heteromers, Microglia, and Neuroprotection
References
Chapter 3: Purinergic Signaling in Brain Physiology
Adenosine Receptors
P2 Receptors
P2X Receptors
P2Y Receptors
P2 Receptors in Neurons and Glia
Presynaptic Receptors
Postsynaptic P2 Receptors
P2 Receptors in Glia Communication
P2 Receptors in Microglia
Conclusion
References
Chapter 4: Neurotrophic Actions of Adenosine and Guanosine: Implications for Neural Development and Regeneration?
Purine Nucleoside Regulation
Purine Nucleoside Receptors
Trophic Actions of Purine Nucleosides
Cell Proliferation
Cell Migration
Cell Differentiation
Neurite Outgrowth
Synaptogenesis
Conclusion
References
Chapter 5: Purinergic Signaling in Neurogenesis and Neural Fate Determination: Current Knowledge and Future Challenges
Neurogenesis
Expression of Purinergic Signaling Elements During Embryogenesis
The Role of Purinergic Signaling in the Proliferation of Stem and Progenitor Cells
The Role of Purinergic Signaling in Progenitor Cell Migration
The Role of Purinergic Signaling in Cell Fate Destination
Neurogenesis in the Postnatal Brain
Purinergic Signaling Role in Neurogenesis of the Subventricular Zone
Purinergic Signaling Role in Neurogenesis of the Dentate Gyrus Subgranular Zone
Novel Strategies to Study Purinergic Role in Neurogenesis and Concluding Remarks
References
Chapter 6: Purinergic Signaling in Autism Spectrum Disorder
Introduction
ASD
Purinergic System and Autism-Like Features
Humans
Animal Models
Purinergic System and Metabolism in ASD
Adenosine
Mitochondria
Data from Humans
Data from Animal Models
Purinergic System and Neuroimmune Aspects in ASD
Purinergic System and Molecular Modulation in ASD
Therapeutic Approaches and Purinergic System in ASD
ADO and P1 Receptor Modulators
CGS 21680
Propentofylline
P2 Receptor Modulators
Suramin
Brilliant Blue G
JNJ-47965567, A438079, OxATP, and A740003
Adenylate Cyclase Modulators
NB001
Diterpenoid Forskolin
Other Types of Therapeutic Molecules
5-Aminolevulinic Acid
Exogenous ATP and UTP
Exogenous UMP and CMP
Concluding Remarks
References
Chapter 7: Purinergic Signaling in Depression
Introduction
Major Depressive Disorder: Brief Overview of Its Epidemiology, Treatment, and Neurobiology
Purinergic Signaling
Adenosine Signaling in Mood Regulation and Mood Disorders
Overview of the Adenosinergic System
Preclinical Evidence
Human Studies
ATP Signaling in Mood Regulation and Mood Disorders
Overview of the ATPergic Signaling in the Brain
ATP Signaling and Brain Neurochemistry
ATP Signaling and Neurogenic Process
ATP Signaling and Neuroplasticity
P2X7 Receptor-Mediated Signaling and NLRP3-IL-1 Inflammasome Liaison
P2 Signaling, Microglia, and Neuroinflammation
P2X7 Receptor Activation by Stress Exposure and the Role of IL-1β as the Mediator
NLRP3 Inflammasome as an Interplay Between P2X7 Receptor Activation and Neuroinflammation
The Canonical and Non-canonical NLRP3 Inflammasome Activation Pathway
Evidence of NLRP3 Inflammasome Involvement in the Effects of P2X7 Receptor Modulation After Stress Exposure
P2X7 and NLRP3 Involvement in Behavioral Changes Induced by Immune Challenge and Other Conditions
Is There Any Evidence of Antidepressant Drug Effects on P2X7 Receptor and NLRP3 Inflammasome?
Targeting P2X7 Receptor in Stress and Depression
Conclusion and Future Perspectives
References
Chapter 8: Roles of Purinergic Receptors in Alzheimer’s Disease
Introduction
Purinergic Signalization in AD
The P2X7 Purinergic Receptor and AD
Involvement of the Adenosinergic Receptor A2A in AD
Conclusions
References
Chapter 9: Purinergic Signaling in Parkinson’s Disease
The Basal Ganglia
Parkinson’s Disease
Purinergic Receptors in Parkinson’s Disease
P1 (Adenosine Receptors)
Expression of Adenosine Receptors in the Brain
A1 Receptors in Parkinson’s Disease
A2A Receptors in Parkinson’s Disease
Treatments with Adenosine Receptor Antagonists for Parkinson’s Disease
P2 Receptors
The P2X4 Receptor
The P2X7 Receptor
The P2Y6 Receptor
The P2Y12 Receptor
Perspectives and Conclusions
References
Chapter 10: A Step in the ALS Direction: Lessons from the Purinome
Introduction: On the Patient’s Side
Contributions of Clinicians and Researchers to ALS
The Disease
Disease Heterogeneity
The Genes
The Mechanisms
Neurodegeneration
Muscle Denervation Atrophy
Neuroinflammation
Proteostasis Dysfunction
The Drugs
The Purinome
Ectonucleotidases
ATP Release Pathways
P1 Receptors
P2 Receptors
P2X7
P2X4, P2Y6, and P2Y12
Conclusions and Future Perspectives: Tampering with the Purinome in ALS
References
Chapter 11: Purinergic P2 Receptors in Epilepsy
Epilepsy and Current Treatment
Current Treatment Strategies for Epilepsy and Seizures
Inflammation and Epilepsy
Animal Models of Epilepsy
ATPergic Signaling in Epilepsy
ATP Release During Seizures and Epilepsy
The Role of P2 Receptors During Seizures and Epilepsy
Ionotropic P2X Receptors
Metabotropic P2Y Receptors
P2 Receptor-Mediated Molecular Mechanisms Contributing to Seizures and Epilepsy
Conclusions and Outlook
References
Chapter 12: Purinergic Signaling in Neuroinflammation
Introduction of Neuroinflammation
Mediators of Pathological Neuroinflammation
Purinergic Signaling Pathways and Neuroinflammation
P2X Receptors
P2Y Receptors
P1 Receptors
Conclusion
Bibliography
Chapter 13: Purinergic Signaling in Brain Tumors
The Brain Tumor: Definition
The Brain as a Metastatic Niche
The Unique Brain Tumor Microenvironment
Purinergic Signaling in Tumor-Associated Macrophage-Microglia Heterogeneity
Protumoral Macrophages
Antitumoral Macrophages
Purinergic System in Microglia
Purinergic Signaling and Cancer Metabolism
Purinergic Signaling in Memory Impairment Caused by Brain Tumors
References
Chapter 14: Development of Purinergic Receptor Agonists and Antagonists
Introduction
Ligand Discovery in the Purinergic System
P2Y Receptor Ligands
P2X Receptor Ligands
Adenosine Receptor Ligands
Conclusions
References
Chapter 15: Acupuncture for Counteracting P2X4 and P2X7 Receptor Involvement in Neuroinflammation
Introduction
Role of P2X4 and P2X7 Receptors in the Control of Neuroinflammation
Acupuncture Therapy and Neuroinflammation
Role of P2X4 and P2X7 Receptors in Acupuncture Controlling Neuroinflammation
Future Work
References
Index
