Contents 1 Metabolism and Roles of Eicosanoids in Brain
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1 Contents 1 Metabolism and Roles of Eicosanoids in Brain Introduction Multiplicity of Cyclooxygenases, Lipoxygenases, and Epoxygenases in the Brain Cyclooxygenases (COXs) Lipoxygenases (LOXs) Cytochrome P450 Epoxygenases (EPOXs) Eicosanoids and Their Receptors in Brain Interplay Among COX, LOX, and EPOX-derived Products, and Relationship to Upstream PLA 2 Isoforms Roles of Eicosanoids in the Brain Eicosanoids in Neuroinflammation Eicosanoids in Neurodegeneration Eicosanoids in Nociception (Pain State) Eicosanoids in Synaptic Plasticity Eicosanoids in Neurotraumatic Diseases Eicosanoids in Ischemic Injury Eicosanoids in Spinal Cord Trauma Eicosanoids in Traumatic Brain Injury Eicosanoids in Epilepsy Eicosanoids in Neurodegenerative Diseases COX, LOX, EPOX, and Eicosanoids in AD COX, LOX, EPOX, and Eicosanoids in PD COX, LOX, EPOX, and Eicosanoids in Amyotrophic Lateral Sclerosis COX, LOX, EPOX, and Eicosanoids in Creutzfeldt-Jakob Disease (CJD) Conclusions References xvii
2 xviii Contents 2 Recent Development on the Neurochemistry of Docosanoids Introduction Importance of n-3 Polyunsaturated Fatty Acids in the Brain EPA-Derived Lipid Mediators in the Brain DHA-Derived Lipid Mediators in the Brain S D Series Resolvins Protectins and Neuroprotectin Conclusion References Metabolism, Roles, and Involvement of Lyso-glycerophospholipids in Neurological Disorders Introduction Deacylation/Reacylation Cycle (Land s Cycle) and Its Importance Acyl-CoA Synthetases in the Brain Acyl-CoA: Lyso-phospholipid Acyltransferase in the Brain Phospholipases A 2 (PLA 2 ) in the Brain Long-Chain Acyl-CoA Hydrolase or Thioesterases in the Brain CoA-independent Reacylation in the Brain Effects of Lysophospholipids on Neural Membrane Metabolism Lysophosphatidylcholine (Lyso-PtdCho) Lyso-phosphatidylethanolamine (Lyso-PtdEtn) Lyso-phosphatidylserine (Lyso-PtdSer) Lyso-phosphatidylinositol (Lyso-PtdIns) Lyso-cardiolipin (Lyso-Ptd 2 Gro) Lyso-ethanolamine and Choline Plasmalogens (Lyso-PlsEtn and Lyso-PlsCho) Lyso-phosphatidic Acid (Lyso-PtdH) Lyso-phospholipids in Neurotraumatic and Neurodegenerative Diseases Lyso-phospholipids in Ischemic Injury Lyso-phospholipids in Alzheimer Disease Lyso-phospholipids in MS and EAE Lyso-phospholipids in NCL Conclusion References... 97
3 Contents xix 4 Platelet-Activating Factor in Brain: Its Metabolism, Roles, and Involvement in Neurological Disorders Introduction PAF Biosynthesis in the Brain De Novo Synthesis of PAF Remodeling Pathway for PAF Synthesis Oxidative Fragmentation Pathway for PAF Synthesis Catabolism of PAF in the Brain PAF Receptors in the Brain PAF in Neurological and Visceral Disorders PAF in Neurological Disorders PAF in Visceral Disorders PAF in Kainic Acid Neurotoxicity Molecular Mechanism Associated with PAF-Mediated Neural Injury Conclusion References Cannabinoids in the Brain: Their Metabolism, Roles, and Involvement in Neurological Disorders Introduction Cannabinoid Receptor-Mediated Signaling in the Brain Occurrence and Synthesis of Endocannabinoids in the Brain Metabolism of 2-Arachidonylglycerol in the Brain Metabolism of Anandamide in the Brain Interplay Among Cannabinoid, Glutamate, and Dopamine Receptors in the Basal Ganglia Endocannabinoids and Neurological Disorders Endocannabinoids in Neurotraumatic Diseases Endocannabinoids in Neurodegenerative Disorders Use of FAAH and MGL Inhibitors for Inflammatory Pain Conclusion References Neurochemical Aspects of 4-Hydroxynonenal Introduction Synthesis of 4-HNE in the Brain Metabolism of 4-HNE in the Brain Effect of 4-HNE on Enzyme Activities Modulation of Kinases by 4-HNE Modulation of Caspases by 4-HNE Modulation of Glutathione S-Transferases by 4-HNE
4 xx Contents Modulation of ATPases by 4-HNE Modulation of Other Enzymes and Cell Cycle by 4-HNE Modulation of Heat Shock Response by 4-HNE Modulation of NMDA Receptor by 4-HNE Modulation of Gene Expression by 4-HNE Modulation of Peroxisomes by 4-HNE Modulation of Nucleic Acid Metabolism by 4-HNE Modulation of Phospholipid Metabolism by 4-HNE Modulation of Blood Brain Barrier by 4-HNE HNE in Neurological Disorders HNE in Alzheimer Diseases HNE in Parkinson Disease HNE in Amyotrophic Lateral Sclerosis HNE in Prion Diseases HNE in Ischemia HNE in Spinal Cord Injury HNE in Traumatic Brain Injury HNE in Kainic Acid Neurotoxicity Hydroxyhexenal (4-HHE) Conclusion References Isoprostanes and Other Nonenzymic Polyunsaturated Fatty Acid-Derived Lipid Mediators in the Brain Introduction Generation of IsoPs in the Brain Degradation of IsoPs in the Brain IsoPs and Signal Transduction Processes IsoPs in Neurodegenerative Diseases IsoPs in Neurotraumatic Diseases NPs in Neurological Disorders Isoketals (Isolevuglandins) in Neurological Disorders Neuroketals in Neurological Disorders Isofurans in Neurological Disorders Neurofurans in Neurological Disorders IsoPs in Kainic Acid Neurotoxicity Conclusion References Ceramide and Ceramide 1 Phosphate in the Brain Introduction Synthesis of Ceramide and Ceramide 1-phosphate in the Brain Degradation of Ceramide and Ceramide 1-phosphate in the Brain
5 Contents xxi 8.4 Roles of Ceramide and Ceramide 1-phosphate in the Brain Ceramide in Neurological Disorders Ceramide in Ischemic Injury Ceramide in Alzheimer Disease Ceramide in Parkinson Disease Ceramide in Amyotrophic Lateral Sclerosis Ceramide in Multiple Sclerosis Ceramide in HIV Ceramide in Batten Disease Ceramide in Major Depressive Disorders Ceramide in Kainic Acid Neurotoxicity Conclusion References Sphingosine and Sphingosine 1 Phosphate in the Brain Introduction Sphingosine Kinases in the Brain Sphingosine 1 Phosphate Receptors in the Brain Sphingosylphosphorylcholine in the Brain FTY720 and Its Neurochemical Effects Sphingosine 1 Phosphate in Neurological Disorders Sphingosine 1 Phosphate in Ischemia Sphingosine 1 Phosphate in Traumatic Brain and Spinal Cord Injuries Sphingosine 1 Phosphate in Alzheimer Disease Sphingosine 1 Phosphate in Multiple Sclerosis Sphingosine 1 Phosphate in Kainic Acid Neurotoxicity Conclusion References Cholesterol and Hydroxycholesterol in the Brain Introduction Synthesis of Cholesterol and Hydroxycholesterols in the Brain Degradation of Cholesterol in the Brain Roles of Hydroxycholesterols in the Brain Hydroxycholesterols in Neural Cell Differentiation Hydroxycholesterols in Exocytosis Hydroxycholesterols in Apoptosis Cholesterol and Hydroxycholesterols in Neurological Disorders Cholesterol and Hydroxycholesterol in Alzheimer Disease Cholesterol and Hydroxycholesterol in Parkinson Disease
6 xxii Contents Cholesterol and Hydroxycholesterol in Huntington Disease Cholesterol and Hydroxycholesterols in Niemann-Pick Type C Cholesterol and Hydroxycholesterol in Multiple Sclerosis Hydroxycholesterol in Traumatic Brain Injury Cholesterol and Hydroxycholesterols in Cerebrotendinous Xanthomatosis Cholesterol and Hydroxycholesterols in Kainic Acid Neurotoxicity Conclusion References Perspective and Direction for Future Studies on Lipid Mediators Introduction Lipid Mediators in the Brain Interactions Among Phospholipid-, Sphingolipid-, and Cholesterol-Derived Lipid Mediators in the Brain Detection and Levels of Lipid Mediators in Neurological Disorders by Lipidomics Modulation of Lipid Mediators by Diet Conclusion References Index
7
386 Index ARA (arachidonic acid) (cont.) in neural membranes, in neuropsychiatric disorders ADHD, 313 aggressive disorders and cocaine addiction
Index A Acrolein non-enzymic oxidation of ARA and, 121 124 See also Enzymic oxidation Acute neural trauma, see Neurotraumatic disorders Acyl-CoA in brain, 64 67 lysophospholipid acyltransferase (ALCAT),
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