What is included with this book?
Contributors | p. xiii |
Preface | p. xxi |
Foreword | p. xxiii |
Inflammatory Mediators Leading to Protein Misfolding and Uncompetitive/Fast Off-Rate Drug Therapy for Neurodegenerative Disorders | |
Introduction | p. 3 |
Protein Misfolding in Neurodegenerative Diseases | p. 5 |
Generation of RNS/ROS | p. 6 |
Protein S-Nitrosylation and Neuronal Cell Death | p. 7 |
Parkin and the UPS | p. 9 |
S-Nitrosylation and Parkin | p. 10 |
The Unfolded Protein Response and PDI | p. 11 |
S-Nitrosylation of PDI Mediates Protein Misfolding and Neurotoxicity in Cell Models of PD or AD | p. 14 |
PDI Activity in ALS and Prion Disease | p. 15 |
Potential Treatment of Excessive NMDA-Induced Ca[superscript 2+] Influx and S-Nitrosylation | p. 16 |
Looking to the Future: NitroMemantines | p. 18 |
Conclusions | p. 19 |
References | p. 20 |
Innate Immunity and Protective Neuroinflammation: New Emphasis on the Role of Neuroimmune Regulatory Proteins | |
Characteristics of the Cellular and Molecular Innate Immune Responses in the Brain | p. 30 |
Innate Immune Response in Health: The Key Role of Physical Barriers | p. 32 |
Immunoprivileged Status of the Brain by Preventing the Infiltration of Potentially Harmful Systemic Immune Cells: Roles of ACAMPs | p. 33 |
Protective Innate Immune Response During Brain Infection and Inflammation to Promote the Clearance of Pathogens: Roles of PAMPs | p. 35 |
Interactions of Innate Immune Molecules with Toxic Proteins: Roles of PPAMPs | p. 36 |
Regulating the Innate Immune Response in the CNS While Promoting Tissue Repair: Roles of Neuroimmune Regulatory Molecules | p. 38 |
Innate Immunity and Neurogenesis | p. 42 |
The Canonical Innate Immune System in the CNS: The Complement System | p. 43 |
Conclusion: Elements to Drive Innate Immune Neuroprotective Activities | p. 45 |
References | p. 47 |
Glutamate Release from Astrocytes in Physiological Conditions and in Neurodegenerative Disorders Characterized by Neuroinflammation | |
Introduction | p. 58 |
Ca[superscript 2+]-Dependent Glutamate Release from Astrocytes | p. 59 |
Excitotoxicity Involving Ca[superscript 2+]-Dependent Glutamate Release from Astrocytes in Pathological Conditions: The Case of ADC | p. 62 |
Astrocytic Alterations and Ca[superscript 2+]-Dependent Glutamate Release Dysfunction in AD | p. 65 |
Conclusions | p. 67 |
References | p. 68 |
The High-Mobility Group Box 1 Cytokine Induces Transporter-Mediated Release of Glutamate from Glial Subcellular Particles (Gliosomes) Prepared from In Situ-Matured Astrocytes | |
Introduction | p. 74 |
Gliosomes as a Model to Study Astrocyte Characteristics | p. 75 |
HMGB1-Induced Glutamate Release from Gliosomes | p. 81 |
Concluding Remarks | p. 88 |
References | p. 90 |
The Role of Astrocytes and Complement System in Neural Plasticity | |
Introduction | p. 96 |
Astrocytes, GFAP, and Astrocyte Intermediate Filaments | p. 96 |
Reactive Gliosis, Neurotrauma, and CNS Transplants | p. 100 |
The Complement System | p. 103 |
References | p. 107 |
New Insights into the Roles of Metalloproteinases in Neurodegeneration and Neuroprotection | |
Introduction | p. 114 |
The NEP Family | p. 115 |
The NEP Homologue ECE-1 | p. 121 |
The ACE Family | p. 123 |
Ischemia/Hypoxia and Ageing as Factors Affecting Metalloproteinases | p. 125 |
Conclusions | p. 127 |
References | p. 128 |
Relevance of High-Mobility Group Protein Box 1 to Neurodegeneration | |
Introduction | p. 137 |
Structure and Nuclear Functions | p. 139 |
Cytokine Functions | p. 140 |
Role of HMGB1 in CNS (DYS)Function | p. 142 |
Conclusions | p. 145 |
References | p. 145 |
Early Upregulation of Matrix Metalloproteinases Following Reperfusion Triggers Neuroinflammatory Mediators in Brain Ischemia in Rat | |
Introduction | p. 150 |
Methods | p. 152 |
Results | p. 156 |
Discussion | p. 161 |
References | p. 164 |
The (Endo)Cannabinoid System in Multiple Sclerosis and Amyotrophic Lateral Sclerosis | |
Introduction | p. 172 |
The ECS | p. 172 |
ECS in MS | p. 173 |
ECS in ALS | p. 176 |
Conclusions | p. 179 |
References | p. 180 |
Chemokines and Chemokine Receptors: Multipurpose Players in Neuroinflammation | |
Introduction | p. 188 |
Fractalkine and Fractalkine Receptor (CX3CR1) Govern Regulatory NK Accumulation and Microglial Activation During Neuroinflammation | p. 191 |
CXCR2 Regulates Both Monocyte Infiltration and Oligodendrocyte-Mediated Tissue Repair in EAE | p. 197 |
References | p. 201 |
Systemic and Acquired Immune Responses in Alzheimer's Disease | |
Alzheimer's Neuropathology | p. 205 |
Cellular Immune Responses | p. 206 |
Humoral Immune Responses in the Periphery | p. 218 |
Conclusion | p. 223 |
References | p. 223 |
Neuroinflammation in Alzheimer's Disease and Parkinson's Disease: Are Microglia Pathogenic in Either Disorder? | |
Introduction | p. 236 |
Neuroinflammation in AD and PD | p. 237 |
PD May Provide a More Facile Model for Demonstrating a Pathogenic Role of Neuroinflammation | p. 237 |
Advantages of Microglial Cell Cultures | p. 238 |
Responses of Cultured Microglia to AD and PD Pathology | p. 239 |
Conclusions | p. 241 |
References | p. 244 |
Cytokines and Neuronal Ion Channels in Health and Disease | |
Introduction | p. 247 |
Properties of Ion Channels | p. 251 |
Distribution and Targeting of Neuronal Ion Channels | p. 251 |
Ion Channels Are Targeted by Proinflammatory Cytokines | p. 252 |
IL-1[beta] and Voltage-Dependent Ca[superscript 2+] Channels | p. 254 |
IL-1[beta] and NMDAR | p. 256 |
TNF-[alpha]: Few Final Considerations | p. 258 |
Conclusions | p. 258 |
References | p. 259 |
Cyclooxygenase-2, Prostaglandin E[subscript 2], and Microglial Activation in Prion Diseases | |
Introduction | p. 266 |
COXs and PGs in Brain Functions | p. 267 |
Prion Diseases | p. 268 |
COXs in Human and Experimental Prion Diseases | p. 270 |
Roles of COX-2 and PGE[subscript 2] in Prion Diseases | p. 272 |
References | p. 273 |
Glia Proinflammatory Cytokine Upregulation as a Therapeutic Target for Neurodegenerative Diseases: Function-Based and Target-Based Discovery Approaches | |
Neuroinflammation and Disease Progression | p. 278 |
CNS Proinflammatory Cytokine Production as a Therapeutic Target for AD | p. 280 |
De Novo Lead Compound Discovery and the Recent Major Changes in Translational Research at the Chemistry-Biology Interface | p. 285 |
Development of Minozac: A Function-Driven Approach to Develop Small Molecule Compounds That Target Proinflammatory Cytokine Upregulation | p. 288 |
References | p. 292 |
Oxidative Stress and the Pathogenesis of Neurodegenerative Disorders | |
Introduction: Free Radicals, Immunity, and the Nervous System | p. 298 |
Neuropathogenesis of Neurodegeneration | p. 301 |
Free Radicals and Neurodegenerative Disorders | p. 306 |
Glutathione System, Glutamate-Glutamine Cycle, and the CNS | p. 308 |
Modulators of Microglial Activation | p. 309 |
Growth Factors, Antioxidants, and Anti-Inflammatory Drug Therapies | p. 313 |
Therapeutic Immunomodulation | p. 315 |
Summary | p. 317 |
References | p. 317 |
Differential Modulation of Type 1 and Type 2 Cannabinoid Receptors Along the Neuroimmune Axis | |
Introduction | p. 328 |
Lipid Rafts and Cannabinoid Receptors | p. 328 |
Discussion | p. 331 |
References | p. 334 |
Effects of the HIV-1 Viral Protein TAT on Central Neurotransmission: Role of Group I Metabotropic Glutamate Receptors | |
Neurological Complications of HIV-1 Infection | p. 340 |
The HIV-1 Viral Protein Tat | p. 341 |
About the Experimental Approach | p. 342 |
Effects of Tat on the Release of Neurotransmitters in CNS | p. 342 |
Effects of Tat on Presynaptic AMPA/Kainate Receptors | p. 344 |
Effects of Tat on Presynaptic NMDA Receptors | p. 344 |
Effects of Tat on Presynaptic Metabotropic Glutamate Receptors | p. 348 |
Specie Specificity of Tat-Mediated Effects and Amino Acid Sequences Involved | p. 352 |
Conclusions | p. 352 |
References | p. 353 |
Evidence to Implicate Early Modulation of Interleukin-1[beta] Expression in the Neuroprotection Afforded by 17[beta]-Estradiol in Male Rats Undergone Transient Middle Cerebral Artery Occlusion | |
Introduction | p. 358 |
Methods | p. 360 |
Results | p. 362 |
Discussion | p. 366 |
References | p. 369 |
A Role for Brain Cyclooxygenase-2 and Prostaglandin-E[subscript 2] in Migraine: Effects of Nitroglycerin | |
Introduction | p. 374 |
Materials and Methods | p. 375 |
Results | p. 376 |
Discussion | p. 377 |
References | p. 380 |
The Blockade of K[superscript +]-ATP Channels Has Neuroprotective Effects in an In Vitro Model of Brain Ischemia | |
Introduction | p. 384 |
Materials and Methods | p. 385 |
Results | p. 387 |
Discussion | p. 391 |
References | p. 393 |
Retinal Damage Caused by High Intraocular Pressure-Induced Transient Ischemia Is Prevented by Coenzyme Q10 in Rat | |
Introduction | p. 398 |
Materials and Methods | p. 398 |
Results | p. 400 |
Discussion | p. 403 |
References | p. 405 |
Evidence Implicating Matrix Metalloproteinases in the Mechanism Underlying Accumulation of IL-1[beta] and Neuronal Apoptosis in the Neocortex of HIV/gp120-Exposed Rats | |
Introduction | p. 408 |
Materials and Methods | p. 409 |
Results | p. 412 |
Discussion | p. 416 |
References | p. 418 |
Neuroprotective Effect of Nitroglycerin in a Rodent Model of Ischemic Stroke: Evaluation of Bcl-2 Expression | |
Introduction | p. 424 |
Materials and Methods | p. 425 |
Results | p. 427 |
Discussion | p. 428 |
References | p. 432 |
Index | p. 437 |
Contents of Recent Volumes | p. 451 |
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