title: Severe alterations in lipid composition of frontal cortex lipid rafts from Parkinson's disease and incidental Parkinson's disease.
abstract: Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein-lipid and protein-protein interactions. We purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson's disease (PD) and incidental Parkinson's disease (iPD) subjects and analyzed their lipid composition. We observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 long-chain polyunsaturated fatty acids, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paralleling these findings, unsaturation and peroxidability indices were considerably reduced in PD and iPD lipid rafts. Lipid classes were also affected in PD and iPD lipid rafts. Thus, phosphatidylserine and phosphatidylinositol were increased in PD and iPD, whereas cerebrosides and sulfatides and plasmalogen levels were considerably diminished. Our data pinpoint a dramatic increase in lipid raft order due to the aberrant biochemical structure in PD and iPD and indicate that these abnormalities of lipid rafts in the frontal cortex occur at early stages of PD pathology. The findings correlate with abnormal lipid raft signaling and cognitive decline observed during the development of these neurodegenerative disorders.
authors: Instituto de Tecnologías Biomédicas, Universidad de La Laguna, Tenerife, Spain.
authors: Noemí
authors: N
authors: Fabelo
authors: Virginia
authors: V
authors: Martín
authors: Gabriel
authors: G
authors: Santpere
authors: Raquel
authors: R
authors: Marín
authors: Laia
authors: L
authors: Torrent
authors: Isidre
authors: I
authors: Ferrer
authors: Mario
authors: M
authors: Díaz
mesh_terms: D000368:Aged; D016718:Arachidonic Acid / Q000032:analysis; D001344:Autopsy; D015153:Blotting, Western; D002554:Cerebrosides / Q000032:analysis; D002849:Chromatography, Gas; D004281:Docosahexaenoic Acids / Q000032:analysis; D005227:Fatty Acids / Q000032:analysis / Q000145:classification; D005260:Female; D005625:Frontal Lobe / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000032:analysis / Q000737:chemistry* / Q000145:classification; D008297:Male; D021962:Membrane Microdomains / Q000737:chemistry* / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D010716:Phosphatidylinositols / Q000032:analysis; D010718:Phosphatidylserines / Q000032:analysis; D010955:Plasmalogens / Q000032:analysis; D013433:Sulfoglycosphingolipids / Q000032:analysis; D013482:Superoxide Dismutase / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2
chemical_list: D016718:Arachidonic Acid; D002554:Cerebrosides; D004281:Docosahexaenoic Acids; D005227:Fatty Acids; D008055:Lipids; D010716:Phosphatidylinositols; D010718:Phosphatidylserines; D010955:Plasmalogens; D013433:Sulfoglycosphingolipids; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000099156:Superoxide Dismutase 2; C000606290:SOD1 protein, human