Neuroinflammation in Neuronal Death and Repair

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  • Edition: 1st
  • Format: Hardcover
  • Copyright: 2007-07-25
  • Publisher: Elsevier Science
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Neuroinflammation has been implicated recently in the pathogenesis of many neurodegenerative diseases. The cross-talk between neurons and non-neuronal cells seems to be a critical step in the progression of neurodegeneration and molecules that have a beneficial role may turn into harmful players. Thus, matrix metalloproteinases (MMPs), which are involved in axonal growth and regeneration as well as synaptic plasticity, may also have detrimental effects. Recent evidence has linked MMPs to conditions like ischemia, multiple sclerosis, Alzheimer's disease and suggested that, together with their role in the degradation of extracellular macromolecules, MMPs could work as important signalling molecules from injured neurons to the microglia. Thus, MMP-3 has been shown to induce the release of pro-inflammatory cytokines from microglia via activation of ERK and NF-kB-dependent pathways. Increasing evidence highlights the importance of a balanced cross-talk between neurons and non-neuronal cells and indicates that the presence of reactive astrocytes, the activation of microglia and the release of inflammatory mediators may contribute to the progression of many central nervous system disorders, independently of the nature of the primary pathogenic event. However, many aspects still remain controversial and much more effort is needed to understand the role of neuroinflammatory mediators and processes in these conditions. This volume brings together renowned, international scientists to discuss current knowledge and views on the mechanisms of neuroinflammation, on its role in the context of different neurodegenerative diseases (i.e. Alzheimer's, prion disease, HIV-associated dementia, multiple sclerosis, pain) and on the potential approaches for future therapeutic strategies.

Table of Contents

Contributorsp. xiii
Prefacep. xxi
Forewordp. xxiii
Inflammatory Mediators Leading to Protein Misfolding and Uncompetitive/Fast Off-Rate Drug Therapy for Neurodegenerative Disorders
Introductionp. 3
Protein Misfolding in Neurodegenerative Diseasesp. 5
Generation of RNS/ROSp. 6
Protein S-Nitrosylation and Neuronal Cell Deathp. 7
Parkin and the UPSp. 9
S-Nitrosylation and Parkinp. 10
The Unfolded Protein Response and PDIp. 11
S-Nitrosylation of PDI Mediates Protein Misfolding and Neurotoxicity in Cell Models of PD or ADp. 14
PDI Activity in ALS and Prion Diseasep. 15
Potential Treatment of Excessive NMDA-Induced Ca[superscript 2+] Influx and S-Nitrosylationp. 16
Looking to the Future: NitroMemantinesp. 18
Conclusionsp. 19
Referencesp. 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 Brainp. 30
Innate Immune Response in Health: The Key Role of Physical Barriersp. 32
Immunoprivileged Status of the Brain by Preventing the Infiltration of Potentially Harmful Systemic Immune Cells: Roles of ACAMPsp. 33
Protective Innate Immune Response During Brain Infection and Inflammation to Promote the Clearance of Pathogens: Roles of PAMPsp. 35
Interactions of Innate Immune Molecules with Toxic Proteins: Roles of PPAMPsp. 36
Regulating the Innate Immune Response in the CNS While Promoting Tissue Repair: Roles of Neuroimmune Regulatory Moleculesp. 38
Innate Immunity and Neurogenesisp. 42
The Canonical Innate Immune System in the CNS: The Complement Systemp. 43
Conclusion: Elements to Drive Innate Immune Neuroprotective Activitiesp. 45
Referencesp. 47
Glutamate Release from Astrocytes in Physiological Conditions and in Neurodegenerative Disorders Characterized by Neuroinflammation
Introductionp. 58
Ca[superscript 2+]-Dependent Glutamate Release from Astrocytesp. 59
Excitotoxicity Involving Ca[superscript 2+]-Dependent Glutamate Release from Astrocytes in Pathological Conditions: The Case of ADCp. 62
Astrocytic Alterations and Ca[superscript 2+]-Dependent Glutamate Release Dysfunction in ADp. 65
Conclusionsp. 67
Referencesp. 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
Introductionp. 74
Gliosomes as a Model to Study Astrocyte Characteristicsp. 75
HMGB1-Induced Glutamate Release from Gliosomesp. 81
Concluding Remarksp. 88
Referencesp. 90
The Role of Astrocytes and Complement System in Neural Plasticity
Introductionp. 96
Astrocytes, GFAP, and Astrocyte Intermediate Filamentsp. 96
Reactive Gliosis, Neurotrauma, and CNS Transplantsp. 100
The Complement Systemp. 103
Referencesp. 107
New Insights into the Roles of Metalloproteinases in Neurodegeneration and Neuroprotection
Introductionp. 114
The NEP Familyp. 115
The NEP Homologue ECE-1p. 121
The ACE Familyp. 123
Ischemia/Hypoxia and Ageing as Factors Affecting Metalloproteinasesp. 125
Conclusionsp. 127
Referencesp. 128
Relevance of High-Mobility Group Protein Box 1 to Neurodegeneration
Introductionp. 137
Structure and Nuclear Functionsp. 139
Cytokine Functionsp. 140
Role of HMGB1 in CNS (DYS)Functionp. 142
Conclusionsp. 145
Referencesp. 145
Early Upregulation of Matrix Metalloproteinases Following Reperfusion Triggers Neuroinflammatory Mediators in Brain Ischemia in Rat
Introductionp. 150
Methodsp. 152
Resultsp. 156
Discussionp. 161
Referencesp. 164
The (Endo)Cannabinoid System in Multiple Sclerosis and Amyotrophic Lateral Sclerosis
Introductionp. 172
The ECSp. 172
ECS in MSp. 173
ECS in ALSp. 176
Conclusionsp. 179
Referencesp. 180
Chemokines and Chemokine Receptors: Multipurpose Players in Neuroinflammation
Introductionp. 188
Fractalkine and Fractalkine Receptor (CX3CR1) Govern Regulatory NK Accumulation and Microglial Activation During Neuroinflammationp. 191
CXCR2 Regulates Both Monocyte Infiltration and Oligodendrocyte-Mediated Tissue Repair in EAEp. 197
Referencesp. 201
Systemic and Acquired Immune Responses in Alzheimer's Disease
Alzheimer's Neuropathologyp. 205
Cellular Immune Responsesp. 206
Humoral Immune Responses in the Peripheryp. 218
Conclusionp. 223
Referencesp. 223
Neuroinflammation in Alzheimer's Disease and Parkinson's Disease: Are Microglia Pathogenic in Either Disorder?
Introductionp. 236
Neuroinflammation in AD and PDp. 237
PD May Provide a More Facile Model for Demonstrating a Pathogenic Role of Neuroinflammationp. 237
Advantages of Microglial Cell Culturesp. 238
Responses of Cultured Microglia to AD and PD Pathologyp. 239
Conclusionsp. 241
Referencesp. 244
Cytokines and Neuronal Ion Channels in Health and Disease
Introductionp. 247
Properties of Ion Channelsp. 251
Distribution and Targeting of Neuronal Ion Channelsp. 251
Ion Channels Are Targeted by Proinflammatory Cytokinesp. 252
IL-1[beta] and Voltage-Dependent Ca[superscript 2+] Channelsp. 254
IL-1[beta] and NMDARp. 256
TNF-[alpha]: Few Final Considerationsp. 258
Conclusionsp. 258
Referencesp. 259
Cyclooxygenase-2, Prostaglandin E[subscript 2], and Microglial Activation in Prion Diseases
Introductionp. 266
COXs and PGs in Brain Functionsp. 267
Prion Diseasesp. 268
COXs in Human and Experimental Prion Diseasesp. 270
Roles of COX-2 and PGE[subscript 2] in Prion Diseasesp. 272
Referencesp. 273
Glia Proinflammatory Cytokine Upregulation as a Therapeutic Target for Neurodegenerative Diseases: Function-Based and Target-Based Discovery Approaches
Neuroinflammation and Disease Progressionp. 278
CNS Proinflammatory Cytokine Production as a Therapeutic Target for ADp. 280
De Novo Lead Compound Discovery and the Recent Major Changes in Translational Research at the Chemistry-Biology Interfacep. 285
Development of Minozac: A Function-Driven Approach to Develop Small Molecule Compounds That Target Proinflammatory Cytokine Upregulationp. 288
Referencesp. 292
Oxidative Stress and the Pathogenesis of Neurodegenerative Disorders
Introduction: Free Radicals, Immunity, and the Nervous Systemp. 298
Neuropathogenesis of Neurodegenerationp. 301
Free Radicals and Neurodegenerative Disordersp. 306
Glutathione System, Glutamate-Glutamine Cycle, and the CNSp. 308
Modulators of Microglial Activationp. 309
Growth Factors, Antioxidants, and Anti-Inflammatory Drug Therapiesp. 313
Therapeutic Immunomodulationp. 315
Summaryp. 317
Referencesp. 317
Differential Modulation of Type 1 and Type 2 Cannabinoid Receptors Along the Neuroimmune Axis
Introductionp. 328
Lipid Rafts and Cannabinoid Receptorsp. 328
Discussionp. 331
Referencesp. 334
Effects of the HIV-1 Viral Protein TAT on Central Neurotransmission: Role of Group I Metabotropic Glutamate Receptors
Neurological Complications of HIV-1 Infectionp. 340
The HIV-1 Viral Protein Tatp. 341
About the Experimental Approachp. 342
Effects of Tat on the Release of Neurotransmitters in CNSp. 342
Effects of Tat on Presynaptic AMPA/Kainate Receptorsp. 344
Effects of Tat on Presynaptic NMDA Receptorsp. 344
Effects of Tat on Presynaptic Metabotropic Glutamate Receptorsp. 348
Specie Specificity of Tat-Mediated Effects and Amino Acid Sequences Involvedp. 352
Conclusionsp. 352
Referencesp. 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
Introductionp. 358
Methodsp. 360
Resultsp. 362
Discussionp. 366
Referencesp. 369
A Role for Brain Cyclooxygenase-2 and Prostaglandin-E[subscript 2] in Migraine: Effects of Nitroglycerin
Introductionp. 374
Materials and Methodsp. 375
Resultsp. 376
Discussionp. 377
Referencesp. 380
The Blockade of K[superscript +]-ATP Channels Has Neuroprotective Effects in an In Vitro Model of Brain Ischemia
Introductionp. 384
Materials and Methodsp. 385
Resultsp. 387
Discussionp. 391
Referencesp. 393
Retinal Damage Caused by High Intraocular Pressure-Induced Transient Ischemia Is Prevented by Coenzyme Q10 in Rat
Introductionp. 398
Materials and Methodsp. 398
Resultsp. 400
Discussionp. 403
Referencesp. 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
Introductionp. 408
Materials and Methodsp. 409
Resultsp. 412
Discussionp. 416
Referencesp. 418
Neuroprotective Effect of Nitroglycerin in a Rodent Model of Ischemic Stroke: Evaluation of Bcl-2 Expression
Introductionp. 424
Materials and Methodsp. 425
Resultsp. 427
Discussionp. 428
Referencesp. 432
Indexp. 437
Contents of Recent Volumesp. 451
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