title: Glycerophospholipids and glycerophospholipid-derived lipid mediators: a complex meshwork in Alzheimer's disease pathology.
abstract: An increasing body of evidence suggested that intracellular lipid metabolism is dramatically perturbed in various cardiovascular and neurodegenerative diseases with genetic and lifestyle components (e.g., dietary factors). Therefore, a lipidomic approach was also developed to suggest possible mechanisms underlying Alzheimer's disease (AD). Neural membranes contain several classes of glycerophospholipids (GPs), that not only constitute their backbone but also provide the membrane with a suitable environment, fluidity, and ion permeability. In this review article, we focused our attention on GP and GP-derived lipid mediators suggested to be involved in AD pathology. Degradation of GPs by phospholipase A(2) can release two important brain polyunsaturated fatty acids (PUFAs), e.g., arachidonic acid and docosahexaenoic acid, linked together by a delicate equilibrium. Non-enzymatic and enzymatic oxidation of these PUFAs produces several lipid mediators, all closely associated with neuronal pathways involved in AD neurobiology, suggesting that an interplay among lipids occurs in brain tissue. In this complex GP meshwork, the search for a specific modulating enzyme able to shift the metabolic pathway towards a neuroprotective role as well as a better knowledge about how lipid dietary modulation may act to slow the neurodegenerative processes, represent an essential step to delay the onset of AD and its progression. Also, in this way it may be possible to suggest new preventive or therapeutic options that can beneficially modify the course of this devastating disease.
authors.affiliation: Department of Geriatrics, Center for Aging Brain, Memory Unit, University of Bari, Bari, Italy. vfrisardi@yahoo.com
authors.forename: Vincenza
authors.initials: V
authors.lastname: Frisardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Panza
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.forename: Tahira
authors.initials: T
authors.lastname: Farooqui
authors.forename: Akhlaq A
authors.initials: AA
authors.lastname: Farooqui
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000544:Alzheimer Disease / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D001095:Arachidonic Acids / Q000737:chemistry / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002186:Cannabinoids / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage* / Q000627:therapeutic use; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000378:metabolism; D020404:Glycerophospholipids / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D008246:Lysophospholipids / Q000378:metabolism; D010084:Oxidation-Reduction; D054467:Phospholipases A2 / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D017382:Reactive Oxygen Species
chemical_list: D000447:Aldehydes; D001095:Arachidonic Acids; D002186:Cannabinoids; D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D020404:Glycerophospholipids; D008246:Lysophospholipids; D010972:Platelet Activating Factor; D017382:Reactive Oxygen Species; D004281:Docosahexaenoic Acids; D054467:Phospholipases A2; C027576:4-hydroxy-2-nonenal