Recent Advances in NGF and Related Molecules: The Continuum of the NGF “Saga”

Preface: Rita Levi-Montalcini
Contents
Part I: Basic Science
	Chapter 1: Nerve Growth Factor: The First Molecule of the Neurotrophin Family
		1.1 Introduction
		1.2 NGF and proNGF: Who Is Doing What?
		1.3 TrkA- and p75NTR-Mediated Intracellular Pathways
		1.4 NGF Target Cells
		References
	Chapter 2: The First and Last Time I Met Rita Levi-Montalcini: From the Insect Neurotrophic Factor to the Nerve Growth Factor ...
		2.1 Introduction
		2.2 How I Met Rita Levi-Montalcini
		2.3 Flight to St. Louis, MO, USA
		2.4 In 1972 RLM Decided to Organize Her Return in Rome
		2.5 NGF and the Central Nervous System
		2.6 Studies on NGF and Clinical Potentiality
		2.7 NGF and Human Corneal Neurotrophic Ulcer
		2.8 NGF and Glaucoma
		2.9 NGF and Macular Degeneration
		2.10 NGF and Cutaneous Wounds
		2.11 Concluding Remarks
		References
	Chapter 3: NGF Signaling in Endosomes
		3.1 Retrograde NGF Signaling Through Endosomes
		3.2 Endocytosis of Neurotrophin-Receptor Complexes in Growth Cones
		3.3 Retrograde Axonal Transport of Signaling Endosomes
		3.4 Biological Functions of Retrograde Signaling Endosomes
		3.5 Generality of Retrograde Signaling Through Endosomes
		3.6 Conclusions
		References
	Chapter 4: The NGF Metabolic Pathway: New Opportunities for Biomarker Research and Drug Target Discovery
		4.1 Introduction
		4.2 Targeting the Cholinergic System in AD: The Value of Symptomatic Treatments
		4.3 NGF Dysmetabolism and the Degeneration of the Cholinergic System in AD: A Self-Propagating  Feedback Loop?
		4.4 The NGF Pathway as a Platform for the Search of New Biomarkers
		4.5 Tracking NGF Metabolism in AD Biofluids
			4.5.1 ProNGF
			4.5.2 tPA and Neuroserpin
			4.5.3 Matrix Metalloproteinase-3 and Metalloproteinase-9
			4.5.4 Correspondence Between NGF Metabolism in Biofluids and the CNS
		4.6 Diagnostic Value of NGF Pathway Biomarkers
		4.7 NGF as a Therapeutic Target in AD
		4.8 Targeting NGF Metabolism
			4.8.1 Restoring Normal Conversion of proNGF to mNGF
			4.8.2 Restoring Normal mNGF Degradation
		4.9 Conclusion
		References
Part II: Development and Regeneration
	Chapter 5: NGF and Endogenous Regeneration: From Embryology Toward Therapies
		5.1 Introduction
		5.2 NGF and Embryonic Development
		5.3 NGF and Epithelial Wound Healing
		5.4 NGF and Axonal Regrowth
		5.5 NGF and Remyelination
		References
	Chapter 6: The Versatile Roles of Nerve Growth Factor in Neuronal Attraction, Odontoblast Differentiation, and Mineral Deposit...
		6.1 Introduction
		6.2 Materials and Methods
			6.2.1 Materials
			6.2.2 Embryonic Human Tissues
			6.2.3 Adult Human Tissues
			6.2.4 Cultures of Human Dental Pulp Cells
			6.2.5 Immunohistochemistry
			6.2.6 Preparation of Microfluidic Devices
			6.2.7 Embryonic Mouse Tissues
			6.2.8 Co-culture of Trigeminal Ganglia and Human Dental Pulp Cells
		6.3 Results
			6.3.1 NGF Distribution in Odontoblasts of Human Embryonic Teeth
			6.3.2 NGF and p75NTR Expression in Intact Functional Human Teeth
			6.3.3 NGF Distribution in Functional Human Teeth After Cavity Preparation
			6.3.4 NGF Expression in Human Dental Pulp Cells In Vitro
			6.3.5 Co-culture of Trigeminal Ganglia and Human Dental Pulp Cells in Microfluidic Devices
		6.4 Discussion
		References
	Chapter 7: An Overview of Adult Neurogenesis
		7.1 Adult Neurogenesis: An Historical Perspective
		7.2 The Doubts Behind Adult Human Neurogenesis
		7.3 Neural Stem Cells
		7.4 Adult Neurogenic Niches
		7.5 The Subventricular Zone (SVZ) Neurogenic Niche
		7.6 The Subgranular Zone (SGZ) Neurogenic Niche
		7.7 Conclusion
		References
	Chapter 8: Intervention of Brain-Derived Neurotrophic Factor and Other Neurotrophins in Adult Neurogenesis
		8.1 Neurotrophins
		8.2 Brain-Derived Neurotrophic Factor (BDNF)
		8.3 Neurotrophin Receptors
		8.4 BDNF Role in Adult Hippocampal Neurogenesis
		8.5 Role of Environmental Factors on BDNF and Adult Hippocampal Neurogenesis
		8.6 BDNF Role in SVZ-Derived Neurogenesis
		8.7 Regulation of Adult Neurogenesis by NGF
		8.8 Regulation of Adult Neurogenesis by NT-3
		8.9 Regulation of Adult Neurogenesis by NT-4
		8.10 Conclusion
		References
Part III: Alzheimer and Central Nervous System
	Chapter 9: Rita Levi-Montalcini, NGF Metabolism in Health and in the Alzheimer´s Pathology
		9.1 Preface
		9.2 What I Knew About Rita During My Early Immersion in the Neurosciences
		9.3 My Encounters with Rita
		9.4 My First Interest in Neural Repair Leading to NGF Research
		9.5 NGF Functions in the Adult Central Nervous System and Reparative Properties for Basal Forebrain Cholinergic Neurons
		9.6 A Novel NGF Metabolic Pathway
			9.6.1 The Background
			9.6.2 The Discovery of the NGF Metabolic Pathway
		9.7 The Deregulation of the NGF Metabolic Pathway in Alzheimer´s Disease and in Down Syndrome
		9.8 The NGF Metabolic Pathway in Health and Disease and Future Challenges
		References
	Chapter 10: NGF and the Amyloid Precursor Protein in Alzheimer´s Disease: From Molecular Players to Neuronal Circuits
		10.1 Alzheimer´s Disease Pathology
		10.2 Past and Current Aetiopathological Hypotheses in Sporadic Alzheimer´s Disease (SAD)
		10.3 BFCNs´ Vulnerability in AD Target Circuits
		10.4 APP and NGF Interplay
			10.4.1 APP Control of the NGF Receptor Trafficking and Signalling
			10.4.2 Bad and Good Interactions of APP with NGF Receptors
			10.4.3 NGF Regulates APP Trafficking and Processing in BFCNs
		10.5 BFCN Insulin Resistance as a Risk Factor for AD. Improvement by NGF
		10.6 Interplay Between MicroRNAs, APP, and NGF in Alzheimer´s Disease
		10.7 Conclusions
		References
	Chapter 11: A Review of Techniques for Biodelivery of Nerve Growth Factor (NGF) to the Brain in Relation to Alzheimer´s Disease
		11.1 Introduction and Background
		11.2 Different Methods of NGF Delivery
			11.2.1 Intracerebroventricular Delivery (ICVD)
			11.2.2 Intracerebral Delivery
				11.2.2.1 Implantation of Tissue Grafts
				11.2.2.2 Intracerebral Infusion
				11.2.2.3 Stem Cell Mediated
				11.2.2.4 Gene Therapy
				11.2.2.5 Encapsulated Biodelivery
			11.2.3 Peripheral Delivery
				11.2.3.1 Intranasal and Intraocular Delivery
				11.2.3.2 Parenteral Delivery
		11.3 Conclusion and Future Developments
		References
	Chapter 12: NGF Released from Blood Cells or Collagen Hydrogels as a Therapeutic Target in Alzheimer´s Disease?
		12.1 Introduction
			12.1.1 Pathology of Alzheimer´s Disease
			12.1.2 NGF and the Cholinergic Neurons in Alzheimer´s Disease
			12.1.3 Delivery of Therapeutics into the Brain
		12.2 Blood Cell-Derived Therapeutics
			12.2.1 Monocytes in the AD Brain
			12.2.2 Platelets in the AD Brain
		12.3 Collagen Hydrogels as Therapeutics
			12.3.1 Collagen Hydrogels in Brain Repair
			12.3.2 NGF Released from Collagen Hydrogels
		12.4 Outlook and Hope
		12.5 Conclusion
		References
Part IV: Complex Behaviors
	Chapter 13: When Nerve Growth Factor Met Behavior
		13.1 Introduction
		13.2 Early Phases of Development: The Mother-Pups Interaction
		13.3 Social Milieu and NGF Release
		13.4 Adrenal Pathway
		13.5 The Most Famous Sibling: The Brain-Derived Neurotrophic (BDNF) Factor
		13.6 Conclusion
		References
	Chapter 14: Cross Talk of BDNF and GDNF in Spinal Substantia Gelatinosa (Lamina II): Focus on Circuitry
		14.1 Introduction
			14.1.1 BDNF and Its Receptors
			14.1.2 GDNF and Its Receptors
		14.2 General Features of the Substantia Gelatinosa
			14.2.1 Neurons of the Substantia Gelatinosa
		14.3 Nociceptive Circuits in Substantia Gelatinosa
			14.3.1 Spinal Somatic Nociceptive Circuits
			14.3.2 Localization of BDNF and Its Preferred Receptor TrkB in DRGs and Dorsal Horn of the Spinal Cord
			14.3.3 Localization of GDNF and GFRα1/Ret in DRGs and the Dorsal Horn of the Spinal Cord
			14.3.4 Role of BDNF and GDNF in Nociception
		14.4 BDNF and GDNF Circuits in the Substantia Gelatinosa
			14.4.1 BDNF and the Excitatory Path
			14.4.2 GDNF and the Inhibitory Path
			14.4.3 Cross Talk Between BDNF and GDNF in Nociceptive Pathways
		14.5 Concluding Remarks
		References
Part V: Clinical Medicine
	Chapter 15: BDNF Gene as a Precision Skill of Obesity Management
		15.1 Introduction
		15.2 Implication of the BDNF in Obesity and Eating Disorders
			15.2.1 Role of BDNF in Energy Homeostasis and Food Intake
			15.2.2 Participation of BDNF on Metabolism
			15.2.3 Genetic Alterations in the Genes Encoding BDNF or Its High-Affinity Receptor TrkB (Tropomyosin-Related Kinase B)
			15.2.4 Epigenetic Programming of BDNF
			15.2.5 BDNF and Hedonic Eating
			15.2.6 BDNF as a Mediator in the Effects of Exercise and Food Intake on Neuroplasticity and the Vulnerability of the Brain and...
		15.3 SNPs of the BDNF Associated with the Obesity
			15.3.1 rs10501087
			15.3.2 rs10767664
			15.3.3 rs11030104
			15.3.4 rs16917237
			15.3.5 rs2030323
			15.3.6 rs6265 (Val66Met)
			15.3.7 rs925946
		15.4 Precision Nutrition for Personalizing Nutritional Recommendations
		15.5 Conclusion and Future Perspectives
		References
	Chapter 16: The Science of Love: State of the Art
		16.1 Introduction
			16.1.1 The First Step of Love: Attraction
			16.1.2 Romantic Attachment
		16.2 Conclusions
		References
	Chapter 17: NGF and Retinitis Pigmentosa: Structural and Molecular Studies
		17.1 Introduction
		17.2 Methods
		17.3 Results
			17.3.1 The Effect of NGF Exposure on Survival of p10 Retinal Cells
			17.3.2 The Effect of NGF on Rhodopsin-Positive Neuritis Outgrowth and trkANGFR Expression
		17.4 Discussion
		References
	Chapter 18: NGF in Inflammatory and Neurodegenerative Diseases of the Eye: New Findings Supporting Neuroprotection and Proper ...
		18.1 Introduction
			18.1.1 NGF and Eye: The Prototype of a Prodigious Family
			18.1.2 NGF and NGF Receptors: Distribution and Function in Posterior Eye Segment
		18.2 NGF and Vitreoretinal Disorders
			18.2.1 NGF as Bystander or Partaker in the Cross Talk Between Resident and Infiltrating Cells
			18.2.2 Neuroprotection: NGF-VEGF Race for RGC, Photoreceptor, Bipolar, and Müller Cell Protection
			18.2.3 Tissue Remodeling: NGF and Extracellular-Matrix Interplay
		18.3 Conclusion and Future Perspectives
		References
Part VI: Veterinary Medicine
	Chapter 19: Nerve Growth Factor (NGF) and Animal Reproduction
		19.1 Introduction
		19.2 Male
			19.2.1 Expression of NGF in Male Accessory Glands
			19.2.2 NGF and Sperm Function
			19.2.3 NGF and Preservation of Spermatozoa
		19.3 Female
			19.3.1 NGF and Ovulation in Females
		19.4 Conclusions
		References
	Chapter 20: Neurotrophins in the Brain of Teleost Fish: The State of the Art
		20.1 Introduction
			20.1.1 Evolutionary Aspects of Fish as Model Organisms in Biomedicine
			20.1.2 The Organization of the Brain of Teleostean Fish
			20.1.3 Comparative Histological Aspects Between the Brain of Teleostean Fish and Mammals
				20.1.3.1 Radial Glia
				20.1.3.2 Oligodendrocytes
				20.1.3.3 Schwann Cells
				20.1.3.4 Microglia
			20.1.4 Neuromediator Systems of Teleostean Fish
		20.2 The Two Mainstream Fish Models in Neurotrophin Research: Zebrafish and the African Turquoise Killifish
			20.2.1 Evolutionary Aspects of Neurotrophins in Teleost Fish
			20.2.2 Neurotrophins in the Brain of Teleost Fish
			20.2.3 bdnf/trkB
			20.2.4 ngf and nt-6/trkA
			20.2.5 nt-3/trkC
			20.2.6 nt-4/5
		20.3 Conclusion and Future Perspectives
		References