Glycerophospholipids in the Brain

Phospholipases A2 in Neurological Disorders

By: Akhlaq A. Farooqui, Lloyd A. Horrocks

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Hardcover | 18 October 2006

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416 Pages

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22.86 x 15.24 x 1.91

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This volume provides readers with a comprehensive description of phospholipid metabolism in brain, activities of phospholipases A2, and their involvement in neurological disorders. The purpose of this book is to present readers with cutting edge information in a lively manner that is useful not only to student and teachers but also to researchers and physicians. This book has 14 chapters that will describe (1) the metabolism in brain of glycerophospholipids, including those containing a vinyl ether group (plasmalogens); (2) cutting edge information on the properties and roles of phospholipases A2 in the central nervous system; (3) the release by phospholipases A2 of second messengers (arachidonic acid, docosahexaenoic acid, and lysophospholipid) from neural membrane phospholipids and their neurochemical effects on brain metabolism and functions; (4) the involvement of phospholipases A2 in neurological and neuropsychiatric disorders, and the use of phospholipase A2 inhibitors for the treatment of diseases associated with altered phospholipid metabolism; and (5) methods for the assays of phospholipases A2 and their clinical significance.

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Non-Fiction Medicine Clinical & Internal Medicine Endocrinology Neurology & Clinical Neurophysiology Science Biology, Life Sciences Life Sciences in General Neurosciences

Phospholipid Metabolism in Brain	p. 1
Introduction	p. 1
Classes, occurrence, and distribution of neural glycerophospholipids	p. 3
Biosynthesis of neural membrane glycerophospholipids	p. 4
Incorporation of glycerophospholipids into neural membranes	p. 8
Effect of structural variations of glycerophospholipids on neural membrane structure	p. 10
Catabolism of neural membrane glycerophospholipids	p. 12
Phospholipid metabolism in the nucleus	p. 14
Roles of glycerophospholipids in brain metabolism	p. 16
Glycerophospholipids as a storag depot for second messengers and their precursors	p. 16
PLA[subscript 2]-generated second messengers	p. 16
PLC-generated second messengers	p. 18
PLD-generated second messengers	p. 18
Involvement of PtdSer and PtdEtn in apoptosis	p. 19
Phosphatidylinositol and membrane anchoring	p. 21
Involvement of glycerophospholipids in regulation of enzymic activities	p. 22
Other roles of glycerophospholipids	p. 23
Conclusion	p. 23
Ether Lipids in Brain	p. 35
General considerations and importance	p. 35
Plasmalogens	p. 37
Biosynthesis	p. 37
Receptor-mediated degradation	p. 38
Roles of plasmalogens in brain tissue	p. 42
Plasmalogens as structural components of neural membranes	p. 43
Plasmalogens as a storage depot for second messengers	p. 43
Plasmalogens and generation of long-chain aldehydes	p. 44
Plasmalogens and membrane fusion	p. 45
Plasmalogens and ion transport	p. 45
Plasmalogen, cholesterol efflux, and atherosclerosis	p. 46
Plasmalogens and their antioxidant activity	p. 47
Plasmalogens in differentiation	p. 48
Platelet-activating factor (PAF)	p. 48
PAF biosynthesis	p. 50
PAF degradation	p. 51
Roles of PAF	p. 52
Antitumor ether lipids	p. 53
Other ether lipids	p. 55
Conclusion	p. 56
Phospholipases A[subscript 2] in Brain	p. 67
Introduction	p. 67
Multiplicity and properties of phospholipase A[subscript 2] in brain tissue	p. 68
sPLA[subscript 2]	p. 68
cPLA[subscript 2]	p. 71
PlsEtn-selective PLA[subscript 2]	p. 76
iPLA[subscript 2]	p. 77
Platelet-activating factor acetylhydrolases (PAF-AH)	p. 80
Other brain phospholipases A[subscript 2]	p. 81
Brain nuclear PLA[subscript 2] activities	p. 82
Regulation of isoforms of PLA[subscript 2] in brain tissue	p. 83
Conclusions	p. 85
Roles of Phospholipases A[subscript 2] in Brain	p. 93
PLA[subscript 2] isoforms and neurotransmitter release	p. 94
PLA[subscript 2] isoforms in long-term potentiation (LTP)	p. 95
Involvement of PLA[subscript 2] isoforms in membrane repair	p. 97
PLA[subscript 2] isoforms in modulation of neurite outgrowth and regeneration	p. 98
PLA[subscript 2] isoforms in inflammatory and anti-inflammatory processes	p. 100
Involvement of PLA[subscript 2] isoforms in the cell cycle	p. 102
PLA[subscript 2] isoforms in tubule formation and membrane trafficking	p. 102
PLA[subscript 2] isoforms in neurodegeneration	p. 104
Involvement of PLA[subscript 2] isoforms in apoptosis	p. 105
Involvement of PLA[subscript 2] isoforms in necrosis	p. 109
Arachidonic Acid and Its Metabolites in Brain	p. 121
Introduction	p. 121
Incorporation of arachidonic acid and docosahexaenoic acid into neural membranes	p. 122
Receptor-mediated release of arachidonic acid	p. 124
Neurotrophic effects of arachidonic acid	p. 129
Neurotoxic effects of arachidonic acid	p. 131
Metabolism of arachidonic acid in brain	p. 132
Importance of eicosanoids in brain	p. 135
Docosahexaenoic Acid and Its Metabolites in Brain	p. 147
Location and turnover of docosahexaenoic acid	p. 147
Incorporation of docosahexaenoic acid	p. 149
Receptor-mediated release of docosahexaenoic acid from glycerophospholipids	p. 151
Effects of DHA and its metaboUtes on brain tissue	p. 153
DHA in gene expression, neurotransmitter release, and enzyme regulation	p. 154
DHA and neurite outgrowth	p. 156
DHA and modulation of learning and memory	p. 157
DHA and apoptotic cell death	p. 158
DHA and generation of docosanoids	p. 159
DHA and the immune response	p. 160
DHA intake, oxidative stress, and other side effects	p. 162
Nonenzymic Metabolites of Arachidonate and Docosahexaenoate in Brain	p. 173
Introduction	p. 173
Reactive oxygen species	p. 173
Lipid hydroperoxides	p. 177
Isoprostanes, isofurans, isothromboxanes, isoleukotrienes, and neuroprostanes	p. 178
Isoprostanes	p. 178
Isothromboxanes	p. 182
Isofurans	p. 183
Isoleukotrienes	p. 184
Neuroprostanes	p. 184
Neuroketals	p. 184
Generation of 4-HNE and its effect on brain metabolism	p. 185
4-HNE is a signaling molecule	p. 185
Neurotoxic effects	p. 186
Effects of acrolein in brain	p. 188
Generation of DHA metabolites and their effect on brain metabolism	p. 189
Neurotrophic effects of DHA	p. 189
Neurotoxic effects of DHA	p. 190
Effects of nonenzymic degradation of LA on brain metabolism	p. 190
Lyso-Glycerophospholipids	p. 199
Introduction	p. 199
Effects of lyso-glycerophospholipids on neural membrane metabolism	p. 201
1-Acyl-2-lyso-sn-GroPCho (Lyso-PtdCho)	p. 201
Lyso-PtdEtn	p. 206
Lyso-PdaSer	p. 206
Lyso-PtdIns	p. 208
Lyso-PlsEtn and lyso-PlsCho	p. 208
Lyso-phospholipases in brain	p. 209
Lyso-plasmalogenase in brain	p. 211
Concluding remarks	p. 212
Lysophosphatidic Acid and Its Metabolism in Brain	p. 219
Functions of lysophosphatidic acid in brain	p. 219
Synthesis and degradation of lyso-PtdH	p. 220
LPA receptors and Lyso-PtdH-mediated signaling in brain	p. 222
Agonists and antagonists of LPA receptors	p. 225
Lyso-PtdH and its receptors in neurological diseases	p. 229
Lyso-PtdH and its receptors in non-neural diseases	p. 230
Involvement of Phospholipids and Phospholipases A[subscript 2] in Neurological Disorders	p. 239
Introduction	p. 239
Similarities and differences between acute neural trauma and neurodegenerative diseases	p. 239
Involvement of excitotoxicity and glycerophospholipid degradation mediated by PLA[subscript 2] in acute neural trauma and neurodegenerative diseases	p. 241
PLA[subscript 2] activity in neurological disorders	p. 243
PLA[subscript 2] in ischemic injury	p. 247
PLA[subscript 2] in Alzheimer disease	p. 250
PLA[subscript 2] in Parkinson disease (PD) and its animal models	p. 254
PLA[subscript 2] in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE)	p. 255
PLA[subscript 2] in prion diseases	p. 257
PLA[subscript 2] in spinal cord injury	p. 258
PLA[subscript 2] in head injury	p. 259
PLA[subscript 2] in epilepsy	p. 259
Excitotoxicity-mediated neurodegeneration involves PLA[subscript 2] activation, generation of lipid mediators, oxidative stress and neuroinflammation	p. 260
Inhibitors of Phospholipases A[subscript 2] and Their Use for the Treatment of Neurological Disorders	p. 275
Introduction	p. 275
Physiological and pharmacological effects of PLA[subscript 2] inhibitors	p. 277
Arachidonoyl trifluoromethyl ketone (AACOCF[subscript 3])	p. 277
Methyl arachidonoyl fluorophosphonate (MAFP)	p. 279
Bromoenol lactone (BEL)	p. 280
Benzenesulfonamides and alkoxybenzamidines	p. 282
3-(Pyrrol)-2-propionic acid	p. 282
2-Oxoamide and 1,3-disubstituted propan-2-ones	p. 282
Choline derivatives with a long aliphatic chain as PLA[subscript 2] inhibitors	p. 283
Pyrrolidine-based inhibitors of PLA[subscript 2]	p. 284
Antimalarial drugs	p. 285
Lithium and carbamazepine	p. 286
Vitamin E and gangliosides	p. 287
Cytidine 5-diphosphoamines (CDP-amines)	p. 289
Long chain polyunsaturated fatty acids	p. 289
PLA[subscript 2] antisense oligonucleotides and interfering RNA (RNAi)	p. 290
Diffusion survival evasion peptide (DSEP)	p. 290
sPLA[subscript 2] inhibitors	p. 291
Annexins (lipocortins)	p. 293
Use of PLA[subscript 2] inhibitors for the treatment of neurological disorders	p. 294
Prevention of pain by PLA[subscript 2] inhibitors	p. 301
Perspective and direction for future studies	p. 302
Assay Methods for Phospholipase A[subscript 2] Activities in Brain	p. 321
Assay methods	p. 321
Titrimetric procedures	p. 322
Radiochemical procedures	p. 323
Spectrophotometric procedures	p. 324
Use of thioester substrate analogs	p. 324
Use of coupled enzyme assays	p. 326
Fluorometric procedures	p. 328
Continuous fluorometric procedures	p. 330
Discontinuous fluorometric procedures	p. 332
Assay of multiple forms of PLA[subscript 2] in biological samples	p. 334
Immunological procedures	p. 335
Glycerophospholipids and Phospholipases A[subscript 2] in Neuropsychiatric Disorders	p. 341
Introduction	p. 341
Schizophrenia	p. 342
Cocaine addiction	p. 345
Depression and bipolar disorders	p. 346
Dyslexia	p. 348
Autism	p. 348
Status of n-3 and n-6 fatty acids in neuropsychiatric disorders	p. 349
Introduction	p. 349
Depression and bipolar disorder	p. 349
Aggressive disorders and cocaine addiction	p. 351
Attention-deficit hyperactivity disorder	p. 351
Effects of n-3 fatty acid supplementation in neuropsychiatric disorders	p. 352
Depression and bipolar disorder	p. 352
Treatment with high-dose EPA	p. 353
ADHD	p. 353
Mechanism of action of n-3 fatty acids	p. 354
Genetic involvement	p. 355
Future Perspectives: Metabolic and Functional Aspects of Neural Membrane Glycerophospholipids	p. 367
Index	p. 377
Table of Contents provided by Ingram. All Rights Reserved.

Glycerophospholipids in the Brain

Phospholipases A2 in Neurological Disorders

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Hardcover

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