Meucci Chemokine Receptors and NeuroAIDS

Beyond Co-Receptor Function and Links to Other Neuropathologies
1. Auflage 2009
ISBN: 978-1-4419-0793-6
Verlag: Springer-Verlag
Format: PDF
Kopierschutz: Wasserzeichen (»Systemvoraussetzungen)

E-Book, Englisch, 412 Seiten

Chemokine Receptors and NeuroAIDS: Beyond the Co-receptor Function and Links to Other Neuropathologies focuses on unresolved or emerging issues concerning the role of chemokine receptors in neuronal injury and HIV neuropathology, including their ability to regulate fundamental neuronal and glial functions and their role in neurovirulence and neurotoxicity. Although the importance of these molecules in the CNS physiology and pathology is now apparent, these issues are still matter of debate, and further research is required to design effective pharmacological agents that specifically target the brain chemokine system without major side effects. To this end, specific topics have been selected and are reviewed by international experts within the basic science/medical community. This book encourages investigation in the most controversial areas and fosters interaction between clinicians and basic scientists. The book also increases awareness about differences in disease progression among different parts of the world as well as selected patient populations, which may also help identifying novel therapeutic strategies.

About the Editor: Olimpia Meucci, MD, PhD is a Professor of Pharmacology and Physiology & Microbiology and Immunology at Drexel University College of Medicine in Philadelphia, PA. Since her seminal discovery about the regulation of neuronal signaling by chemokines, her research has primarily focused on the physio-pathological roles of this important class of neuroimmune modulators in the central nervous system and their involvement in neuroAIDS. These studies have significantly contributed to current understanding of the cellular and molecular mechanisms of HIV-related neuropathology including the interaction of the chemokine system with drug of abuse, namely opiates, which continues to be a major area of investigation in the Meucci lab.

Autoren/Hrsg.

Meucci, Olimpia

Inhaltsverzeichnis

1;Meucci_FM_O.pdf;1
1.1;Anchor 1;5
1.2;Anchor 2;7
1.3;Anchor 3;10
2;Meucci_Ch01_O.pdf;14
2.1;Chapter 1;14
2.1.1;Introduction;14
3;Meucci_Ch02_O.pdf;16
3.1;Chapter 2;17
3.1.1;HIV Neuroinvasion: Early Events, Late Manifestations;17
3.1.1.1;2.1 .Clinical Manifestations and Epidemiology of HIV Infection of the Nervous System;17
3.1.1.2;2.2 .Biology of HIV Infection and Invasion of the Brain;19
3.1.1.3;2.3 .HIV Neuropathogenesis: Human and Primate Studies;21
3.1.1.4;2.4 .Mechanisms of HIV-Induced Neurodegeneration: Neurotoxicity of HIV Proteins;24
3.1.1.5;2.5 .Mechanisms of HIV-Induced Neurodegeneration: Roles for Chemokines and Chemokine Receptors;26
3.1.1.6;2.6 .Mechanisms of HIV-Induced Neurodegeneration: Roles for Excitotoxins and N-Methyl-.d.-Aspartate Receptors;28
3.1.1.7;2.7 .Other Links Between Chemokines and Excitotoxic Injury: Glutamate Release;30
3.1.1.8;2.8 .Therapeutic Considerations;31
3.1.2;References;32
4;Meucci_Ch03_O.pdf;44
4.1;Chapter 3;44
4.1.1;HIV Co-receptors: The Brain Perspective;44
4.1.1.1;.Chemokines as Co-receptors for HIV Infection;44
4.1.1.1.1;3.1.1 .CD4;44
4.1.1.1.2;3.1.2 .Discovery of Chemokine Receptors as “Second Receptors” for HIV-1 Infection;44
4.1.1.2;3.2 .Chemokines and Chemokine Receptors as Determinants of HIV-1 Infection and Disease;45
4.1.1.2.1;3.2.1 .Chemokines and Chemokine Receptors in HIV-1 Transmission;45
4.1.1.2.2;3.2.2 .Chemokines and Chemokine Receptors and HIV-1 Disease Progression;46
4.1.1.2.3;3.2.3 .Chemokines and Response to HAART Therapy;47
4.1.1.2.4;3.2.4 .Chemokines as a Double-Edged Sword in HIV-1 Infection;48
4.1.1.3;3.3 .Chemokines and Chemokine Receptors in HIV-1-Associated CNS Disease;48
4.1.1.3.1;3.3.1 .Direct Mechanisms of Neuronal Injury and Apoptosis;49
4.1.1.3.2;3.3.2 .Indirect Mechanisms of Neuronal Injury and Apoptosis;51
4.1.1.3.2.1;3.3.2.1 .Monocyte/Macrophage Recruitment;51
4.1.1.3.2.2;3.3.2.2 .Impaired Astrocyte Function and Chemokine Expression;52
4.1.1.4;3.4 .Chemokines/Chemokine Receptor Pathways as Survival Pathways for Monocyte/Macrophage Reservoirs of HIV Infection;53
4.1.1.5;3.5 .Chemokines/Chemokine Receptor Based Therapeutics: Trials and Tribulations;54
4.1.2;References;55
5;Meucci_Ch04_O.pdf;62
5.1;Chapter 4;62
5.1.1;HIV Infection and the PNS;62
5.1.1.1;4.1 .Introduction;62
5.1.1.2;4.2 .General Principles in HIV Neurological Disease;62
5.1.1.3;4.3 .Recognizing Peripheral Nervous System Involvement in HIV;63
5.1.1.4;4.4 .Prevalence and Risk Factors of HIV-Associated Peripheral Neuropathy;66
5.1.1.5;4.5 .Distal Symmetric Polyneuropathy;67
5.1.1.6;4.6 .Antiretroviral Toxic Neuropathy;68
5.1.1.7;4.7 .Neuropathies Associated With HIV Seroconversion;69
5.1.1.8;4.8 .Inflammatory Demyelinating Polyradiculoneuropathies;69
5.1.1.9;4.9 .Mononeuropathy Multiplex;70
5.1.1.10;4.10 .Progressive Polyradiculopathy;71
5.1.1.11;4.11 .Diffuse Infiltrative Lymphocytosis Syndrome;72
5.1.1.12;4.12 .Autonomic Neuropathy;73
5.1.1.13;4.13 .Neuropathies Associated with Immune Reconstitution;73
5.1.1.14;4.14 .Motor Neuron Disease;74
5.1.1.15;4.15 .Pathology of HIV-Associated Peripheral Neuropathy;74
5.1.1.16;4.16 .The Role of Chemokine Receptors in HIV Neuropathogenesis;78
5.1.1.17;4.17 .Direct and Indirect Mechanisms of Neurotoxicity;79
5.1.1.18;4.18 .Pathology of Antiretroviral Toxic Neuropathy;82
5.1.1.19;4.19 .The Role of Chemokine Receptors in Neuropathic Pain;84
5.1.1.20;4.20 .Models of HIV-Associated Peripheral Neuropathy;85
5.1.1.21;4.21 .Treatment of HIV-Associated Peripheral Neuropathy;87
5.1.1.22;4.22 .Conclusion;88
5.1.2;References;88
6;Meucci_Ch05_O.pdf;97
6.1;Chapter 5;97
6.1.1;HIV Latency and Reactivation: Role in Neuropathogenesis;97
6.1.1.1;5.1 .Introduction;97
6.1.1.2;5.2 .Types of Latency and Major Cellular Reservoirs;97
6.1.1.2.1;5.2.1 .Pre-integration Latency;98
6.1.1.2.2;5.2.2 .Post-integration Latency and the Resting CD4+ T Cell;100
6.1.1.2.3;5.2.3 .Monocyte–Macrophage Latency;103
6.1.1.2.4;5.2.4 .Cells of the CNS;106
6.1.1.2.5;5.2.5 .Dendritic Cells;107
6.1.1.2.6;5.2.6 .Bone Marrow Cell Populations;108
6.1.1.2.7;5.2.7 .Other Potential Minor Reservoirs;109
6.1.1.3;5.3 .Maintenance of Latency;109
6.1.1.3.1;5.3.1 .Chromatin Determinants;110
6.1.1.3.2;5.3.2 .Availability of Cellular Transcription Factors;113
6.1.1.3.3;5.3.3 .Availability of Viral Proteins;113
6.1.1.4;5.4 .RNA Interference;115
6.1.1.5;5.5 .Neuropathogenesis and Reseeding from Reservoirs;115
6.1.1.6;5.6 .Concluding Remarks;117
6.1.2;References;118
7;Meucci_Ch06_O.pdf;129
7.1;Chapter 6;129
7.1.1;HIV Coreceptors and Their Roles in Leukocyte Trafficking During Neuroinflammatory Diseases;129
7.1.1.1;6.1 .Overview;129
7.1.1.2;6.2 .Leukocyte Trafficking into the CNS;130
7.1.1.3;6.3 .NeuroAIDS;133
7.1.1.3.1;6.3.1 .Human Studies;134
7.1.1.3.2;6.3.2 .Macaque Model;135
7.1.1.4;6.4 .CNS Autoimmunity;135
7.1.1.4.1;6.4.1 .CXCL12 and CXCR4;136
7.1.1.4.2;6.4.2 .CCR5 and Its Ligands;138
7.1.1.5;6.5 .West Nile Virus Encephalitis;142
7.1.1.5.1;6.5.1 .CXCL12 and CXCR4;142
7.1.1.5.2;6.5.2 .CCR5;143
7.1.1.6;6.6 .Conclusions;145
7.1.2;References;146
8;Meucci_Ch07_O.pdf;157
8.1;Chapter 7;158
8.1.1;Chemokine Proteolytic Processing in HIV Infection: Neurotoxic and Neuroimmune Consequences;158
8.1.1.1;7.1 .Introduction;158
8.1.1.2;7.2 .Chemokine Proteolysis Overview;159
8.1.1.3;7.3 .Chemokine Proteolysis Altering HIV Binding to Its Coreceptors;162
8.1.1.3.1;7.3.1 .HIV-Induced Proteases;162
8.1.1.3.1.1;7.3.1.1 .MMPs;163
8.1.1.3.1.2;7.3.1.2 .CD26/DPP IV;164
8.1.1.3.1.3;7.3.1.3 .Cathepsins;165
8.1.1.3.2;7.3.2 .Regulation of Anti-HIV Properties of Chemokines by Limited Proteolysis;165
8.1.1.4;7.4 .Role of Chemokine Proteolysis in HIV Neuropathogenesis: CXCL12 and MMPs;166
8.1.1.4.1;7.4.1 .MMP-Mediated CXCL12 Processing in the Brain Associated with HIV Infection;166
8.1.1.4.1.1;7.4.1.1 .CXCL12 Cleavage by MMPs;166
8.1.1.4.1.2;7.4.1.2 .MMP Processing of CXCL12 is Associated with a Shift of Receptor Affinity from CXCR4 to CXCR3;168
8.1.1.4.2;7.4.2 .Pathogenic Effects of MMP-Processed CXCL12 on Neurons;170
8.1.1.4.2.1;7.4.2.1 .Perturbation of Neuronal Membrane Physiology;170
8.1.1.4.2.2;7.4.2.2 .Neurotoxicity of the MMP-Processed CXCL12;170
8.1.1.4.3;7.4.3 .Immunogenic Properties of MMP-Processed CXCL12 on Glial Cells;171
8.1.1.4.4;7.4.4 .MMP-Processed CXCL12 Effects in an In Vivo Model;172
8.1.1.4.5;7.4.5 .Evolutionary Advantages for the Virus;173
8.1.1.5;7.5 .Concluding Remarks;174
8.1.2;References;175
9;Meucci_Ch08_O.pdf;182
9.1;Chapter 8;182
9.1.1;Chemokines and Chemokine Receptors in the Brain;182
9.1.1.1;8.1 .Introduction;182
9.1.1.2;8.2 .Expression of Chemokines and Their Receptors in the CNS;182
9.1.1.2.1;8.2.1 .Chemokine Receptor Expression in the CNS;182
9.1.1.2.1.1;8.2.1.1 .CCR Family;183
9.1.1.2.1.2;8.2.1.2 .CXCR Family;183
9.1.1.2.1.3;8.2.1.3 .CX3CR1;186
9.1.1.2.2;8.2.2 .Chemokine Expression in the CNS;187
9.1.1.2.2.1;8.2.2.1 .CC Chemokines;187
9.1.1.2.2.2;8.2.2.2 .CXC Chemokines;187
9.1.1.2.2.3;8.2.2.3 .CX3CL1;188
9.1.1.3;8.3 .Role of Chemokines in Regulating CNS Activity;188
9.1.1.4;8.4 .Neuromodulatory Action of Chemokines;190
9.1.1.4.1;8.4.1 .Effect on Neurotransmission;190
9.1.1.4.2;8.4.2 .Involvement of Chemokines in Nociception;191
9.1.1.5;8.5 .Conclusions and Perspectives;194
9.1.2;References;194
10;Meucci_Ch09_O.pdf;199
10.1;Chapter 9;199
10.1.1;Chemokine Signaling in the Nervous System and Its Role in Development and Neuropathology;199
10.1.1.1;9.1 .Introduction;199
10.1.1.2;9.2 .Chemokines and the Development of the Nervous System;200
10.1.1.3;9.3 .The Role of Chemokines in the Control of Adult Neurogenesis;207
10.1.1.4;9.4 .Chemokine Signaling in Pathological Pain States;213
10.1.1.5;9.5 .Conclusions;221
10.1.2;References;221
11;Meucci_Ch10_O.pdf;229
11.1;Chapter 10;229
11.1.1;Modulation of Neuronal Cell Cycle Proteins by Chemokine Receptors and Its Role in the Survival of Postmitotic Neurons;229
11.1.1.1;10.1 .Introduction;229
11.1.1.2;10.2 .General Structure of Chemokines and Their Receptors;229
11.1.1.3;10.3 .Receptor Dynamics;230
11.1.1.3.1;10.3.1 .Receptor Oligomerization;230
11.1.1.3.2;10.3.2 .Ligand Receptor Binding;232
11.1.1.3.2.1;10.3.2.1 .CXCR4;232
11.1.1.3.2.2;10.3.2.2 .CCR5;232
11.1.1.3.2.3;10.3.2.3 .CCR2;233
11.1.1.3.2.4;10.3.2.4 .CXCR3;234
11.1.1.3.3;10.3.3 .Regulation of Signaling;234
11.1.1.3.3.1;10.3.3.1 .CXCR4;234
11.1.1.3.3.2;10.3.3.2 .CCR5;235
11.1.1.3.3.3;10.3.3.3 .CCR2;236
11.1.1.3.3.4;10.3.3.4 .CXCR3;236
11.1.1.4;10.4 .Physiological Roles of Chemokine Receptor Signaling in Nervous System;237
11.1.1.4.1;10.4.1 .Roles of CXCR4 During CNS Development;237
11.1.1.4.2;10.4.2 .Roles of CXCR4 in Mature CNS;239
11.1.1.5;10.5 .Role of CCR5 and CXCR4 in AIDS Neuropathogenesis;239
11.1.1.5.1;10.5.1 .Chemokine Receptor Activation by HIV Envelope Protein gp120;240
11.1.1.5.2;10.5.2 .HIV Envelope gp120 – Mediated SignalingPathways in CNS;241
11.1.1.5.3;10.5.3 .Role of Cell Cycle Proteins in Chemokine Receptor-Mediated Neuronal Survival;243
11.1.1.5.4;10.5.4 .A Comparison Between CXCL12 and gp120 Signaling;245
11.1.1.6;10.6 .Role of CXCR3 and CCR2 in NeuroAIDS;246
11.1.1.6.1;10.6.1 .CXCR3;246
11.1.1.6.2;10.6.2 .CCR2;247
11.1.1.7;10.7 .Conclusions;247
11.1.2;References;248
12;Meucci_Ch11_O.pdf;260
12.1;Chapter 11;260
12.1.1;Chemokines and Primary Brain Tumors;260
12.1.1.1;11.1 .The Prognostic Significance of CXCL12 and CXCR4 Expression in Brain Tumors;260
12.1.1.2;11.2 .CXCR4 Activity Stimulates Brain Tumor Growth Through Diverse Mechanisms;263
12.1.1.2.1;11.2.1 .CXCR4 and Brain Tumor Stem Cells;263
12.1.1.2.2;11.2.2 .CXCL12 Stimulates Brain Tumor Cell Proliferation and Survival;265
12.1.1.3;11.3 .CXCL12 Functions as a Migratory/Invasive Factor for Brain Tumor Cells;268
12.1.1.4;11.4 .CXCR4 and Angiogenesis;269
12.1.1.5;11.5 .Therapeutic Targeting of Chemokine Pathways;270
12.1.1.6;11.6 .Other Chemokines Contribute to Brain Tumor Biology;271
12.1.1.7;11.7 .Conclusions and Future Directions;272
12.1.2;References;273
13;Meucci_Ch12_O.pdf;278
13.1;Chapter 12;278
13.1.1;Chemokines as Neuromodulators: Regulation of Glutamatergic Transmission by CXCR4-Mediated Glutamate Release From Astrocytes;278
13.1.1.1;12.1 .The CXCL12/CXCR4 Signaling Pathway In the Central Nervous System (CNS);278
13.1.1.1.1;12.1.1 .The Expression of CXCL12/CXCR4 System In the CNS;278
13.1.1.1.2;12.1.2 .The Effect of CXCR4-Mediated Signaling Pathway on Neuronal Activity and Neurotransmitter Release;280
13.1.1.1.3;12.1.3 .Activation of CXCR4 Induces Release of Chemical Transmitters (Gliotransmitters) from Glial Cells;282
13.1.1.2;12.2 .Regulated Exocytosis of Glutamate from Astrocytes can Modulate Synaptic Transmission;284
13.1.1.2.1;12.2.1 .Mechanisms of Gliotransmitters Release: Evidence on CXCR4-Mediated Glutamate Exocytosis from Astrocytes;284
13.1.1.2.2;12.2.2 .Localized Calcium Microdomains Control Exocytosis of Glutamate in Astrocytes;288
13.1.1.2.3;12.2.3 .Glutamate Exocytosis from Astrocytes Induces Synaptic Modulation;291
13.1.1.3;12.3 .The Calcium-Dependent Glutamate Release From Astrocytes is Deregulated in Pathological Conditions With an Inflammatory C;292
13.1.1.3.1;12.3.1 .The Case of HIV-Associated Dementia;293
13.1.1.3.2;12.3.2 .The Case of Alzheimer’s Disease;295
13.1.2;References;297
14;Meucci_Ch13_O.pdf;308
14.1;Chapter 13;308
14.1.1;Role of CX3CL1 in Synaptic Activity and Neuroprotection;308
14.1.1.1;13.1 .Introduction;308
14.1.1.1.1;13.1.1 .CX3CL1/CX3CR1 Pair: Structure and Signalling;308
14.1.1.1.2;13.1.2 .Distribution in the Nervous System;309
14.1.1.2;13.2 .CX3CL1 Functions in Physiological and Pathological Conditions;310
14.1.1.2.1;13.2.1 .CX3CL1 and Synaptic Activity;310
14.1.1.2.2;13.2.2 .CX3CL1 and Pain Modulation;312
14.1.1.2.3;13.2.3 .CX3CL1 and Neuroprotection;314
14.1.1.2.3.1;13.2.3.1 .HIV Infection;315
14.1.1.2.3.2;13.2.3.2 .Glutamate Excitotoxicity and Models of Brain Ischemia;315
14.1.1.2.3.3;13.2.3.3 .Modulatory Effects on Neuronal Precursors;317
14.1.1.2.3.4;13.2.3.4 .Neuroinflammation and Neurodegeneration Models;317
14.1.1.3;13.3 .CX3CL1 as Mediators of Intercellular Communication in the Nervous System;318
14.1.2;References;319
15;Meucci_Ch14_O.pdf;324
15.1;Chapter 14;325
15.1.1;Interaction Between Opioid and Chemokine Receptors in Immune Cells: Implications for HIV Infection;325
15.1.1.1;14.1 .Introduction;325
15.1.1.2;14.2 .Regulation of Chemokine Expression by Opioids;327
15.1.1.3;14.3 .Regulation of Chemokine Receptor Expression by Opioids;330
15.1.1.4;14.4 .Cross-talk Between Opioid and Chemokine Receptors;333
15.1.1.4.1;14.4.1 .Certain Chemokine Receptors Cross-Desensitize Opioid Receptors;333
15.1.1.4.2;14.4.2 .Opioid Receptors Cross-Desensitize Chemokine Receptors;335
15.1.1.4.3;14.4.3 .Molecular Mechanism of Heterologous Desensitization between Opioid and Chemokine Receptors;336
15.1.1.4.4;14.4.4 .Implications for HIV Infection;336
15.1.1.5;14.5 .Conclusions;337
15.1.2;References;338
16;Meucci_Ch15_O.pdf;342
16.1;Chapter 15;342
16.1.1;Chronic Morphine’s Role on Innate Immunity, Bacterial Susceptibility and Implications in Wound Healing;342
16.1.1.1;15.1 .Introduction;342
16.1.1.2;15.2 .Wound Healing and Innate Immunity;342
16.1.1.2.1;15.2.1 .Pro-inflammatory Response;342
16.1.1.2.2;15.2.2 .Pro-angoigenic Response;344
16.1.1.3;15.3 .Opioids;345
16.1.1.3.1;15.3.1 .Endogenous Opioids;346
16.1.1.3.2;15.3.2 .Exogenous Opioids;346
16.1.1.3.3;15.3.3 .Opioid Antagonists;347
16.1.1.4;15.4 .Opioids and Innate Immunity;347
16.1.1.4.1;15.4.1 .Morphine and Immunosuppression;347
16.1.1.4.2;15.4.2 .Morphine and Neutrophils;347
16.1.1.4.3;15.4.3 .Morphine and Macrophages;348
16.1.1.4.4;15.4.4 .Morphine and Wound Healing;349
16.1.1.5;15.5 .HIV and Innate Immunity;350
16.1.1.5.1;15.5.1 .HIV and Macrophages: The Trojan Horse;350
16.1.1.5.2;15.5.2 .HIV and the Host Innate Immunity Response;351
16.1.1.5.3;15.5.3 .Opioids, HIV and Wound Healing;351
16.1.1.6;15.6 .Proposed Model;352
16.1.1.7;15.7 .Summary;353
16.1.2;References;353
17;Meucci_Ch16_O.pdf;358
17.1;Chapter 16;358
17.1.1;Opioids, Astroglial Chemokines, Microglial Reactivity, and Neuronal Injury in HIV-1 Encephalitis;358
17.1.1.1;16.1 .Introduction;358
17.1.1.1.1;16.1.1 .The Endogenous Opioid System;358
17.1.1.2;16.2 .Opioid–Chemokine Interactions;359
17.1.1.2.1;16.2.1 .Chemokine Ligands and Receptors;359
17.1.1.2.2;16.2.2 .Pain/Nociception;359
17.1.1.3;16.3 .NeuroAIDS;360
17.1.1.3.1;16.3.1 .Glia are the Principal Targets of HIV in the CNS;360
17.1.1.4;16.4 .Opiate–Immune Interactions in the Brain are Unique;361
17.1.1.5;16.5 .Microglia;363
17.1.1.5.1;16.5.1 .Opioids and Microglia;363
17.1.1.5.2;16.5.2 .Neuron-Microglia Chemokine Signaling;365
17.1.1.6;16.6 .Astroglia;365
17.1.1.6.1;16.6.1 .Astroglia and HIV-1;366
17.1.1.7;16.7 .Opioids, HIV, and Astroglial-derived Chemokines;367
17.1.2;References;370
18;Meucci_Ch17_O.pdf;383
18.1;Chapter 17;383
18.1.1;Regulation of Neuronal Chemokine Receptor CXCR4 by .m.-Opioid Agonists and Its Involvement in NeuroAIDS;383
18.1.1.1;17.1 .CXCR4 and Opioid Receptors in the CNS: Distribution, Signaling, and Involvement in Neuropathology;383
18.1.1.2;17.2 .Heterologous Desensitization of G-protein-Coupled Chemokine Receptors;385
18.1.1.3;17.3 .Cross-talk Between Opioid and Chemokine Receptors;387
18.1.1.4;17.4 .Opioid–Chemokine Interaction in HIV Neuropathology;392
18.1.1.5;17.5 .Concluding Remarks;394
18.1.2;References;395
19;Meucci_BM1_O.pdf;402
19.1;Anchor 1;402
19.2;Anchor 2;403
20;Meucci_Index_O.pdf;404