Glycerophospholipids in the Brain (eBook)

Preface 5
Contents 7
Abbreviations 13
Nomenclature of Glycerophospholipids 14
References 15
Phospholipid Metabolism in Brain 16
1.1 Introduction 16
1.2 Classes, Occurrence, and Distribution of Neural Glycerophospholipids 18
1.3 Biosynthesis of Neural Membrane Glycerophospholipids 19
1.4 Incorporation of Glycerophospholipids into Neural Membranes 23
1.5 Effect of Structural Variations of Glycerophospholipids on Neural Membrane Structure 25
1.6 Catabolism of Neural Membrane Glycerophospholipids 27
1.7 Phospholipid Metabolism in the Nucleus 29
1.8 Roles of Glycerophospholipids in Brain Metabolism 31
1.8.1 Glycerophospholipids as a Storage Depot for Second Messengers and Their Precursors 31
1.8.2 Involvement of PtdSer and PtdEtn in Apoptosis 34
1.8.3 Phosphatidylinositol and Membrane Anchoring 36
1.8.4 Involvement of Glycerophospholipids in Regulation of Enzymic Activities 37
1.8.5 Other Roles of Glycerophospholipids 38
1.9 Conclusion 38
References 39
Ether Lipids in Brain 50
2.1 General Considerations and Importance 50
2.2 Plasmalogens 52
2.2.1 Biosynthesis 52
2.2.2 Receptor-Mediated Degradation 53
2.2.3 Roles of Plasmalogens in Brain Tissue 57
2.2.4 Plasmalogen, Cholesterol Efflux, and Atherosclerosis 61
2.2.5 Plasmalogens and Their Antioxidant Activity 62
2.2.6 Plasmalogens in Differentiation 63
2.3 Platelet-Activating Factor (PAF) 63
2.3.1 PAF Biosynthesis 65
2.3.2 PAF Degradation 66
2.3.3 Roles of PAF 67
2.4 Antitumor Ether Lipids 68
2.5 Other Ether Lipids 70
2.6 Conclusion 71
References 72
Phospholipases A2 in Brain 82
3.1 Introduction 82
3.2 Multiplicity and Properties of Phospholipase A2 in Brain Tissue 83
3.2.1 sPLA2 83
3.2.2 cPLA2 86
3.2.3 PlsEtn-Selective PLA2 91
3.2.4 iPLA2 92
3.3 Platelet-Activating Factor Acetylhydrolases (PAF-AH) 95
3.4 Other Brain Phospholipases A2 96
3.5 Brain Nuclear PLA2 Activities 97
3.6 Regulation of Isoforms of PLA2 in Brain Tissue 98
3.7 Conclusions 100
References 101
Roles of Phospholipases A2 in Brain 108
4.1 PLA2 Isoforms and Neurotransmitter Release 109
4.2 PLA2 Isoforms in Long-Term Potentiation (LTP) 110
4.3 Involvement of PLA2 Isoforms in Membrane Repair 112
4.4 PLA2 Isoforms in Modulation of Neurite Outgrowth and Regeneration 113
4.5 PLA2 Isoforms in Inflammatory and Anti-Inflammatory Processes 115
4.6 Involvement of PLA2 Isoforms in the Cell Cycle 117
4.7 PLA2 Isoforms in Tubule Formation and Membrane Trafficking 117
4.8 PLA2 Isoforms in Neurodegeneration 119
4.8.1 Involvement of PLA2 Isoforms in Apoptosis 120
4.8.2 Involvement of PLA2 Isoforms in Necrosis 124
References 125
Arachidonic Acid and its Metabolites in Brain 135
5.1 Introduction 135
5.2 Incorporation of Arachidonic Acid and Docosahexaenoic Acid into Neural Membranes 136
5.3 Receptor-Mediated Release of Arachidonic Acid 138
5.4 Neurotrophic Effects of Arachidonic Acid 143
5.5 Neurotoxic Effects of Arachidonic Acid 145
5.6 Metabolism of Arachidonic Acid in Brain 146
5.7 Importance of Eicosanoids in Brain 149
References 151
Docosahexaenoic Acid and its Metabolites in Brain 161
6.1 Location and Turnover of Docosahexaenoic Acid 161
6.2 Incorporation of Docosahexaenoic Acid 163
6.3 Receptor-Mediated Release of Docosahexaenoic Acid from Glycerophospholipids 165
6.4 Effects of DHA and its Metabolites on Brain Tissue 167
6.4.1 DHA in Gene Expression, Neurotransmitter Release, and Enzyme Regulation 168
6.4.2 DHA and Neurite Outgrowth 170
6.4.3 DHA and Modulation of Learning and Memory 171
6.4.4 DHA and Apoptotic Cell Death 172
6.4.5 DHA and Generation of Docosanoids 173
6.4.6 DHA and the Immune Response 174
6.4.7 DHA Intake, Oxidative Stress, and Other Side Effects 176
References 177
Nonenzymic Metabolites of Arachidonate and Docosahexaenoate in Brain 187
7.1 Introduction 187
7.2 Reactive Oxygen Species 187
7.3 Lipid Hydroperoxides 191
7.4 Isoprostanes, Isofurans, Isothromboxanes, Isoleukotrienes, and Neuroprostanes 192
7.4.1 Isoprostanes 192
7.4.2 Isothromboxanes 196
7.4.3 Isofurans 197
7.4.4 Isoleukotrienes 198
7.4.5 Neuroprostanes 198
7.4.5 Neuroketals 198
7.5 Generation of 4-HNE and its Effect on Brain Metabolism 199
7.5.1 4-HNE is a Signaling Molecule 199
7.5.2 Neurotoxic Effects 200
7.6 Effects of Acrolein in Brain 202
7.7 Generation of DHA Metabolites and Their Effect on Brain Metabolism 203
7.7.1 Neurotrophic Effects of DHA 203
7.7.2 Neurotoxic Effects of DHA 204
7.8 Effects of Nonenzymic Degradation of LA on Brain Metabolism 204
References 205
Lyso-Glycerophospholipids 212
8.1 Introduction 212
8.2 Effects of Lyso-Glycerophospholipids on Neural Membrane Metabolism 214
8.2.1 1-Acyl-2-lyso-sn-GroPCho (Lyso-PtdCho) 214
8.2.2 Lyso-PtdEtn 219
8.2.3 Lyso-PtdSer 219
8.2.4 Lyso-PtdIns 221
8.2.5 Lyso-PlsEtn and Lyso-PlsCho 221
8.3 Lyso-Phospholipases in Brain 222
8.4 Lyso-Plasmalogenase in Brain 224
8.5 Concluding Remarks 225
References 225
Lysophosphatidic Acid and its Metabolism in Brain 232
9.1 Functions of Lysophosphatidic Acid in Brain 232
9.2 Synthesis and Degradation of lyso-PtdH 233
9.3 LPA Receptors and Lyso-PtdH-Mediated Signaling in Brain 235
9.4 Agonists and Antagonists of LPA Receptors 238
9.5 Lyso-PtdH and its Receptors in Neurological Diseases 242
9.6 Lyso-PtdH and its Receptors in Non-Neural Diseases 243
References 245
Involvement of Phospholipids and Phospholipases A2 in Neurological Disorders 251
10.1 Introduction 251
10.2 Similarities and Differences Between Acute Neural Trauma and Neurodegenerative Diseases 251
10.3 Involvement of Excitotoxicity and Glycerophospholipid Degradation Mediated by PLA2 in Acute Neural Trauma and Neurodegenerative Diseases 253
10.3.1 PLA2 Activity in Neurological Disorders 255
10.3.2 PLA2 in Ischemic Injury 259
10.3.3 PLA2 in Alzheimer Disease 262
10.3.4 PLA2 in Parkinson Disease (PD) and its Animal Models 266
10.3.5 PLA2 in Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE) 267
10.3.6 PLA2 in Prion Diseases 269
10.3.7 PLA2 in Spinal Cord Injury 270
10.3.8 PLA2 in Head Injury 271
10.3.9 PLA2 in Epilepsy 271
10.4 Excitotoxicity-Mediated Neurodegeneration Involves PLA2 Activation, Generation of Lipid Mediators, Oxidative Stress, and Neuroinflammation 272
References 274
Inhibitors of Phospholipases A2 and Their Use for the Treatment of Neurological Disorders 287
11.1 Introduction 287
11.2 Physiological and Pharmacological Effects of PLA Inhibitors 289
11.2.1 Arachidonoyl Trifluoromethyl Ketone (AACOCF3) 289
11.2.2 Methyl Arachidonoyl Fluorophosphonate (MAFP) 291
11.2.3 Bromoenol Lactone (BEL) 292
11.2.4 Benzenesulfonamides and Alkoxybenzamidines 294
11.2.5 3-(Pyrrol)-2-propionic Acid 294
11.2.6 2-Oxoamide and 1,3-Disubstituted Propan-2-ones 294
11.2.7 Choline Derivatives with a Long Aliphatic Chain as PLA2 Inhibitors 295
11.2.8 Pyrrolidine-Based Inhibitors of PLA2 296
11.2.9 Antimalarial Drugs 297
11.2.10 Lithium and Carbamazepine 298
11.2.11 Vitamin E and Gangliosides 299
11.2.12 Cytidine 5-Diphosphoamines (CDP-amines) 301
11.2.13 Long-Chain Polyunsaturated Fatty Acids 301
11.2.14 PLA2 Antisense Oligonucleotides and Interfering RNA (RNAi) 302
11.2.15 Diffusion Survival Evasion Peptide (DSEP) 302
11.2.16 sPLA2 Inhibitors 303
11.2.17 Annexins (Lipocortins) 305
11.3 Use of PLA2 Inhibitors for the Treatment of Neurological Disorders 306
11.4 Prevention of Pain by PLA2 Inhibitors 313
11.5 Perspective and Direction for Future Studies 314
References 316
Assay Methods for Phospholipase A2 Activities in Brain 332
12.1 Assay Methods 332
12.2 Titrimetric Procedures 333
12.3 Radiochemical Procedures 334
12.4 Spectrophotometric Procedures 335
12.4.1 Use of Thioester Substrate Analogs 335
12.4.2 Use of Coupled Enzyme Assays 337
12.5 Fluorometric Procedures 339
12.5.1. Continuous Fluorometric Procedures 341
12.5.2. Discontinuous Fluorometric Procedures 343
12.6. Assay of Multiple Forms of PLA2 in Biological Samples 345
12.6.1. Immunological Procedures 346
References 347
Glycerophospholipids and Phospholipases A2 in Neuropsychiatric Disorders 352
13.1 Introduction 352
13.2 Schizophrenia 353
13.3 Cocaine Addiction 356
13.4 Depression and Bipolar Disorders 357
13.5 Dyslexia 359
13.6 Autism 359
13.7 Status of n-3 and n-6 Fatty Acids in Neuropsychiatric Disorders 360
13.7.1 Introduction 360
13.7.2 Depression and Bipolar Disorder 360
13.7.3 Aggressive Disorders and Cocaine Addiction 362
13.7.4 Attention-Deficit Hyperactivity Disorder 362
13.8 Effects of n-3 Fatty Acid Supplementation in Neuropsychiatric Disorders 363
13.8.1 Depression and Bipolar Disorder 363
13.8.2 Treatment with High-Dose EPA 364
13.8.3 ADHD 364
13.8.4 Mechanism of Action of n-3 Fatty Acids 365
13.8.5 Genetic Involvement 366
References 367
Future Perspectives: Metabolic and Functional Aspects of Neural Membrane Glycerophospholipids 378
References 384
Colour Plate 388
Index 390