Glycerophospholipids in the brain : phospholipases A₂ in neurological disorders / Akhlaq A. Farooqui and Lloyd A. Horrocks.

Format:

Book

Author/Creator:

Farooqui, Akhlaq A.

Contributor:

Horrocks, Lloyd A.

Language:

English

Subjects (All):

Neurochemistry.

Brain--Metabolism.

Brain.

Phospholipids--Metabolism.

Phospholipids.

Phospholipase A2.

Brain--Diseases--Molecular aspects.

Brain--metabolism.

Glycerophospholipids--metabolism.

Nervous System Diseases.

Phospholipases A.

Brain--Diseases.

Medical Subjects:

Brain--metabolism.

Glycerophospholipids--metabolism.

Nervous System Diseases.

Phospholipases A.

Physical Description:

xvi, 394 pages : illustrations ; 25 cm

Place of Publication:

New York, NY : Springer, [2007]

Summary:

Glycerophospholipids in Brain: Phospholipases A[subscript 2] in Neurological Disorders provides a synthesis of material on the metabolism of phospholipids in the brain which has previously only been available in a scattered number of original papers and reviews. Here, the research of over 25 years is collected in one volume from two of the leading researchers in the field-Akhlaq A. Farooqui and Lloyd A. Horrocks.

Glycerophospholipids in Brain: Phospholipases A[subscript 2] in Neurological Disorders comprehensively describes: metabolism in brain of glycerophospholipids, including those containing a vinyl ether group (plasmalogens), cutting-edge information on the properties and roles of phospholipases A[subscript 2] in the central nervous system, release by phospholipases A[subscript 2] of second messengers (arachidonic acid, docosahexaenoic acid, and lysophospholipid) from neural membrane phospholipids and their neurochemical effects on brain metabolism and function, involvement of phospholipases A[subscript 2] in neurological and neuropsychiatric disorders, and the use of phospholipase A[subscript 2] inhibitors for the treatment of diseases associated with altered phospholipid metabolism, methods for the assays of phospholipases A[subscript 2] and their clinical significance.

This unique volume will be invaluable not only to those interested in biochemical properties of phospholipases A[subscript 2], but also their involvement in neurological disorders. Students will benefit from it as a supplement for a range of neuroscience courses. Clinicians will find it invaluable as well for understanding molecular aspects of neurodegeneration in acute neural trauma (stroke) and neurodegenerative diseases (Alzheimer disease) that are mediated by phospholipases A[subscript 2].

The information in Glycerophospholipids in Brain: Phospholipases A[subscript 2] in Neurological Disorders is presented in a lively manner that has never been attempted until now in this specialized format. It will be the essential text for the authoritative in the field.

Contents:

1 Phospholipid Metabolism in Brain 1

1.2 Classes, occurrence, and distribution of neural glycerophospholipids 3

1.3 Biosynthesis of neural membrane glycerophospholipids 4

1.4 Incorporation of glycerophospholipids into neural membranes 8

1.5 Effect of structural variations of glycerophospholipids on neural membrane structure 10

1.6 Catabolism of neural membrane glycerophospholipids 12

1.7 Phospholipid metabolism in the nucleus 14

1.8 Roles of glycerophospholipids in brain metabolism 16

1.8.1 Glycerophospholipids as a storag depot for second messengers and their precursors 16

1.8.1a PLA[subscript 2]-generated second messengers 16

1.8.1b PLC-generated second messengers 18

1.8.1c PLD-generated second messengers 18

1.8.2 Involvement of PtdSer and PtdEtn in apoptosis 19

1.8.3 Phosphatidylinositol and membrane anchoring 21

1.8.4 Involvement of glycerophospholipids in regulation of enzymic activities 22

1.8.5 Other roles of glycerophospholipids 23

2 Ether Lipids in Brain 35

2.1 General considerations and importance 35

2.2 Plasmalogens 37

2.2.1 Biosynthesis 37

2.2.2 Receptor-mediated degradation 38

2.2.3 Roles of plasmalogens in brain tissue 42

2.2.3a Plasmalogens as structural components of neural membranes 43

2.2.3b Plasmalogens as a storage depot for second messengers 43

2.2.3c Plasmalogens and generation of long-chain aldehydes 44

2.2.3d Plasmalogens and membrane fusion 45

2.2.3e Plasmalogens and ion transport 45

2.2.4 Plasmalogen, cholesterol efflux, and atherosclerosis 46

2.2.5 Plasmalogens and their antioxidant activity 47

2.2.6 Plasmalogens in differentiation 48

2.3 Platelet-activating factor (PAF) 48

2.3.1 PAF biosynthesis 50

2.3.2 PAF degradation 51

2.3.3 Roles of PAF 52

2.4 Antitumor ether lipids 53

2.5 Other ether lipids 55

3 Phospholipases A[subscript 2] in Brain 67

3.2 Multiplicity and properties of phospholipase A[subscript 2] in brain tissue 68

3.2.1 sPLA[subscript 2] 68

3.2.2 cPLA[subscript 2] 71

3.2.3 PlsEtn-selective PLA[subscript 2] 76

3.2.4 iPLA[subscript 2] 77

3.3 Platelet-activating factor acetylhydrolases (PAF-AH) 80

3.4 Other brain phospholipases A[subscript 2] 81

3.5 Brain nuclear PLA[subscript 2] activities 82

3.6 Regulation of isoforms of PLA[subscript 2] in brain tissue 83

4 Roles of Phospholipases A[subscript 2] in Brain 93

4.1 PLA[subscript 2] isoforms and neurotransmitter release 94

4.2 PLA[subscript 2] isoforms in long-term potentiation (LTP) 95

4.3 Involvement of PLA[subscript 2] isoforms in membrane repair 97

4.4 PLA[subscript 2] isoforms in modulation of neurite outgrowth and regeneration 98

4.5 PLA[subscript 2] isoforms in inflammatory and anti-inflammatory processes 100

4.6 Involvement of PLA[subscript 2] isoforms in the cell cycle 102

4.7 PLA[subscript 2] isoforms in tubule formation and membrane trafficking 102

4.8 PLA[subscript 2] isoforms in neurodegeneration 104

4.8.1 Involvement of PLA[subscript 2] isoforms in apoptosis 105

4.8.2 Involvement of PLA[subscript 2] isoforms in necrosis 109

5 Arachidonic Acid and Its Metabolites in Brain 121

5.2 Incorporation of arachidonic acid and docosahexaenoic acid into neural membranes 122

5.3 Receptor-mediated release of arachidonic acid 124

5.4 Neurotrophic effects of arachidonic acid 129

5.5 Neurotoxic effects of arachidonic acid 131

5.6 Metabolism of arachidonic acid in brain 132

5.7 Importance of eicosanoids in brain 135

6 Docosahexaenoic Acid and Its Metabolites in Brain 147

6.1 Location and turnover of docosahexaenoic acid 147

6.2 Incorporation of docosahexaenoic acid 149

6.3 Receptor-mediated release of docosahexaenoic acid from glycerophospholipids 151

6.4 Effects of DHA and its metaboUtes on brain tissue 153

6.4.1 DHA in gene expression, neurotransmitter release, and enzyme regulation 154

6.4.2 DHA and neurite outgrowth 156

6.4.3 DHA and modulation of learning and memory 157

6.4.4 DHA and apoptotic cell death 158

6.4.5 DHA and generation of docosanoids 159

6.4.6 DHA and the immune response 160

6.4.7 DHA intake, oxidative stress, and other side effects 162

7 Nonenzymic Metabolites of Arachidonate and Docosahexaenoate in Brain 173

7.2 Reactive oxygen species 173

7.3 Lipid hydroperoxides 177

7.4 Isoprostanes, isofurans, isothromboxanes, isoleukotrienes, and neuroprostanes 178

7.4.1 Isoprostanes 178

7.4.2 Isothromboxanes 182

7.4.3 Isofurans 183

7.4.4 Isoleukotrienes 184

7.4.5 Neuroprostanes 184

7.4.5 Neuroketals 184

7.5 Generation of 4-HNE and its effect on brain metabolism 185

7.5.1 4-HNE is a signaling molecule 185

7.5.2 Neurotoxic effects 186

7.6 Effects of acrolein in brain 188

7.7 Generation of DHA metabolites and their effect on brain metabolism 189

7.7.1 Neurotrophic effects of DHA 189

7.7.2 Neurotoxic effects of DHA 190

7.8 Effects of nonenzymic degradation of LA on brain metabolism 190

8 Lyso-Glycerophospholipids 199

8.2 Effects of lyso-glycerophospholipids on neural membrane metabolism 201

8.2.1 1-Acyl-2-lyso-sn-GroPCho (Lyso-PtdCho) 201

8.2.2 Lyso-PtdEtn 206

8.2.3 Lyso-PdaSer 206

8.2.4 Lyso-PtdIns 208

8.2.5 Lyso-PlsEtn and lyso-PlsCho 208

8.3 Lyso-phospholipases in brain 209

8.4 Lyso-plasmalogenase in brain 211

9 Lysophosphatidic Acid and Its Metabolism in Brain 219

9.1 Functions of lysophosphatidic acid in brain 219

9.2 Synthesis and degradation of lyso-PtdH 220

9.3 LPA receptors and Lyso-PtdH-mediated signaling in brain 222

9.4 Agonists and antagonists of LPA receptors 225

9.5 Lyso-PtdH and its receptors in neurological diseases 229

9.6 Lyso-PtdH and its receptors in non-neural diseases 230

10 Involvement of Phospholipids and Phospholipases A[subscript 2] in Neurological Disorders 239

10.2 Similarities and differences between acute neural trauma and neurodegenerative diseases 239

10.3 Involvement of excitotoxicity and glycerophospholipid degradation mediated by PLA[subscript 2] in acute neural trauma and neurodegenerative diseases 241

10.3.1 PLA[subscript 2] activity in neurological disorders 243

10.3.2 PLA[subscript 2] in ischemic injury 247

10.3.3 PLA[subscript 2] in Alzheimer disease 250

10.3.4 PLA[subscript 2] in Parkinson disease (PD) and its animal models 254

10.3.5 PLA[subscript 2] in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) 255

10.3.6 PLA[subscript 2] in prion diseases 257

10.3.7 PLA[subscript 2] in spinal cord injury 258

10.3.8 PLA[subscript 2] in head injury 259

10.3.9 PLA[subscript 2] in epilepsy 259

10.4 Excitotoxicity-mediated neurodegeneration involves PLA[subscript 2] activation, generation of lipid mediators, oxidative stress and neuroinflammation 260

11 Inhibitors of Phospholipases A[subscript 2] and Their Use for the Treatment of Neurological Disorders 275

11.2 Physiological and pharmacological effects of PLA[subscript 2] inhibitors 277

11.2.1 Arachidonoyl trifluoromethyl ketone (AACOCF[subscript 3]) 277

11.2.2 Methyl arachidonoyl fluorophosphonate (MAFP) 279

11.2.3 Bromoenol lactone (BEL) 280

11.2.4 Benzenesulfonamides and alkoxybenzamidines 282

11.2.5 3-(Pyrrol)-2-propionic acid 282

11.2.6 2-Oxoamide and 1,3-disubstituted propan-2-ones 282

11.2.7 Choline derivatives with a long aliphatic chain as PLA[subscript 2] inhibitors 283

11.2.8 Pyrrolidine-based inhibitors of PLA[subscript 2] 284

11.2.9 Antimalarial drugs 285

11.2.10 Lithium and carbamazepine 286

11.2.11 Vitamin E and gangliosides 287

11.2.12 Cytidine 5-diphosphoamines (CDP-amines) 289

11.2.13 Long chain polyunsaturated fatty acids 289

11.2.14 PLA[subscript 2] antisense oligonucleotides and interfering RNA (RNAi) 290

11.2.15 Diffusion survival evasion peptide (DSEP) 290

11.2.16 sPLA[subscript 2] inhibitors 291

11.2.17 Annexins (lipocortins) 293

11.3 Use of PLA[subscript 2] inhibitors for the

treatment of neurological disorders 294

11.4 Prevention of pain by PLA[subscript 2] inhibitors 301

11.5 Perspective and direction for future studies 302

12 Assay Methods for Phospholipase A[subscript 2] Activities in Brain 321

12.1 Assay methods 321

12.2 Titrimetric procedures 322

12.3 Radiochemical procedures 323

12.4 Spectrophotometric procedures 324

12.4.1 Use of thioester substrate analogs 324

12.4.2 Use of coupled enzyme assays 326

12.5 Fluorometric procedures 328

12.5.1 Continuous fluorometric procedures 330

12.5.2 Discontinuous fluorometric procedures 332

12.6 Assay of multiple forms of PLA[subscript 2] in biological samples 334

12.6.1 Immunological procedures 335

13 Glycerophospholipids and Phospholipases A[subscript 2] in Neuropsychiatric Disorders 341

13.2 Schizophrenia 342

13.3 Cocaine addiction 345

13.4 Depression and bipolar disorders 346

13.5 Dyslexia 348

13.6 Autism 348

13.7 Status of n-3 and n-6 fatty acids in neuropsychiatric disorders 349

13.7.2 Depression and bipolar disorder 349

13.7.3 Aggressive disorders and cocaine addiction 351

13.7.4 Attention-deficit hyperactivity disorder 351

13.8 Effects of n-3 fatty acid supplementation in neuropsychiatric disorders 352

13.8.1 Depression and bipolar disorder 352

13.8.2 Treatment with high-dose EPA 353

13.8.3 ADHD 353

13.8.4 Mechanism of action of n-3 fatty acids 354

13.8.5 Genetic involvement 355

14 Future Perspectives: Metabolic and Functional Aspects of Neural Membrane Glycerophospholipids 367.

Notes:

Includes bibliographical references and index.

ISBN:

0387366024

9780387366029

OCLC:

78070266