Purinergic Signaling in Neurodevelopment, Neuroinflammation and Neurodegeneration

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