Metabolism and Functions of Bioactive Ether Lipids in the Brain

Occurrence and importance of ether lipids in brain.- Introduction.- Classification of ether lipids found in brain.- Physicochemical properties of ether lipids.- Fecapentaenes, the novel plasmalogens.- Other ether lipid found in mammalian tissues.- Lipid metabolism in ether lipid-deficient mice.- Conclusion.- Biosynthesis of plasmalogens in brain.- General considerations and distribution of plasmalogens in brain.- Biosynthesis of plasmalogens.- Dihydroxyacetone phosphate acyltransferase.- Alkyl-dihydroxyacetone phosphate synthase.- Acyl/alkyl dihydroxyacetone phosphate reductase 2.2.4. Alkyl-GP acyltransferase.- Alkylacyl-GP phosphohydrolase.- CDP-ethanomamine: diacylglycerol ethanolaminephosphotransferase.- Plasmalogen synthesizing enzymes during brain development.- Topology and distribution of plasmalogen and plasmalogen synthesizing enzymes.- Plasmalogens in lipid rafts.- Plasmalogens in the nucleus.- Factors affecting plasmalogen biosynthesis in brain.- Conclusion.- Catabolism of plasmalogens in brain.- Introduction.- Plasmalogen-selective phospholipase A2.- Receptor-mediated degradation of plasmalogens.- Regulation of PlsEtn-PLA2.- Turnover of Plasmalogen in brain.- Remodeling of plasmalogens (Reacylation/deacylation reactions).- Degradation of plasmalogens by phospholipase C.- Non-enzymic oxidation of plasmalogens in brain.- Plasmalogen-derived lipid mediators and their importance in brain.- Lysoplasmalogens in brain.- Conclusion.- Assay and purification of plasmalogen-selective phospholipase A2 and lysoplasmalogenase activities.- Introduction.- Determination of PlsEtn and PlsCho-PLA2 by radiochemical procedures.- Preparation of radiolabled [3H] plasmenylcholine (choline plasmalogen).- Labeling of lysoplasmenylcholine at the sn-2 position.- Determination of PlsCho-PLA2activity.- Determination of PlsEtn-PLA2 by fluorometric assay.- Purification of ethanolamine plasmalogen.- Labeling of ethanolamine plasmalogen with pyrenesulfonyl chloride.- Determination of PlsEtn-PLA2 activity with pyrene-labeled plasmalogen.- Continuous spectrophotometric determination of PlsEtn-PLA2.- Determination of lysoplasmalogenase.- Continuous spectrophotometric procedure for lysoplasmalogenase.- Continuous spectrofluorometric procedure for lysoplasmalogenase.- Activities of plasmalogen-selective PLA2 in brains of various animal species and cultured cells of neuronal and glial origin.- Determination of lysoplasmalogenase activity in rat liver and brain microsomes.- Purification of plasmalogen-selective PLA2 from brain.- Purification of lysoplasmalogenase from liver.- Conclusion.- Roles of plasmalogens in brain.- Introduction.- Roles of plasmalogens in brain.- Plasmalogens as neural membrane components.- Plasmalogens as a storage depot for second messengers.- Plasmalogens in regulation of enzymic activities.- Plasmalogens in membrane fusion.- Plasmalogens in ion transport.- Plasmalogens in high density lipoprotein.- Plasmalogen, cholesterol oxidation, efflux and atherosclerosis.- Plasmalogens and their antioxidant activity.- Plasmalogen and generation of long-chain aldehydes.- Plasmalogen in differentiation.- Plasmalogens in ocular development.- Plasmalogens as precursors for PAF.- Conclusion.- Involvement of plasmalogens in neurological disorders.- Introduction.- Plasmalogens in neurological disorders.- Plasmalogens in ischemic injury.- Plasmalogens in Alzheimer disease.- Plasmalogens in spinal cord injury.- Plasmalogens in peroxisomal disorders.- Plasmalogens in Sjogren-Larsson syndrome.- Plasmalogens in malnutrition.- Plasmalogens in fetal alcohol syndrome.- Plasmalogens in diabetic heart.- Plasmalogens in other neurological disorders.- Plasmalogens in uraemic patients.- Plasmalogens in myelin-deficient mutant mice.- Conclusion.- Synthesis of platelet activating factor in brain.- Introduction.- Biosynthesis of platelet activating factor.- Remodeling pathway.- Cytosolic phospholipase A2.- Acetyl CoA: lyso-PAF acetyltransferase.- CoA-independent transacetylase.- De novo synthesis of PAF.- 1-Alkyl-2-lyso-sn-glycero-3-phosphate: acetyl-CoA acetyltransferase.- 1-Alkyl-2-acetyl-sn-glycero-3-phosphate phosphohydrolase.- 1-Alkyl-2-acetyl sn- glycerol: CDP-choline phosphotransferase.- Oxidative fragmentation pathway for PAF synthesis.-  Regulation of PAF synthesis.- Conclusion.- Degradation of platelet activating factor in brain.- Introduction.- PAF acetyl hydrolases in brain and plasma.- Purification and properties of PAF acetyl hydrolases.- Type I PAF acetyl hydrolase in mammalian tissues.- Type II PAF acetyl hydrolase in mammalian tissues.- PAF-acetyl hydrolases in mammalian plasma.- Other PAF acetyl hydrolases.- Regulation and role of PAF acetyl hydrolases in brain.- PAF hydrolyzing phospholipase C.- Other PAF hydrolyzing lipases.- Conclusion.- Roles of platelet activating factor in brain.- Introduction.- PAF receptors in brain.- Translocation of PAF from synthetic site to cell surface receptors.- PAF-receptor-mediated signal transduction.- Roles of platelet activating factor in brain.- PAF in gene expression.- PAF in neural cell migration.- PAF in long-term potentiation.- PAF in glutamate-mediated neurotoxicity.- PAF and calcium influx.- PAF in neuroinflammation.- PAF in cerebral blood flow and blood brain barrier permeability.- PAF in apoptosis.-  PAF in nociception.-  PAF in immune response.- Conclusion.- Involvement of platelet activating factor in neurological disorders.-  Introduction.- Involvement of platelet-activating factor in neurological disorders.- PAF in ischemia.- PAF in traumatic brain and spinal cord injury.- PAF in meningitis.-  PAF in HIV infection.- PAF in prion diseases.- PAF in multiplesclerosis.- PAF in Miller-Dieker lissencephaly.- PAF in migraine attacks.- PAF in kainic acid-mediated neurodegeneration.- Involvement of PAF in non-neural injuries.- Consequences of altered PAF acetyl hydrolase in cardiovascular system.- Molecular mechanism of PAF-mediated neural injury.- Clinical application of PAF antagonists for the treatment of neurological disorders.- Conclusion.- Biochemical effects of non-physiological antitumor ether lipids.- Introduction.- Effect of AEL on enzymes involved in signal transduction.- Effects of AEL on phospholipases A2, C., and D.- Effects of AEL on protein and lipid kinases.- Effect of AEL on cellular receptors.- Other effects of AEL on cellular metabolism.- Molecular mechanism and site of action of AEL.- Conclusion.- Perspective and directions for future development on ether lipids.- Introduction.- Interactions among glycerophospholipid, sphingolipid, and cholesterol-derived lipid mediators.-  Interactions between ether lipid and sphingolipid-derived lipid mediators.- Interactions between sphingolipid and cholesterol-derived lipid mediators.- Use of lipidomics, proteomics, and genomics for characterization of enzymes, lipid mediators, and signal transduction process in normal and diseased brain tissues.- Use of RNAi for the treatment of ether lipid-related neurodegenerative diseases.-  Conclusion