title: Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses.
abstract: Bis(monoacylglycero)phosphate (BMP) is a negatively charged glycerophospholipid with an unusual sn-1;sn-1' structural configuration. BMP is primarily enriched in endosomal/lysosomal membranes. BMP is thought to play a role in glycosphingolipid degradation and cholesterol transport. Elevated BMP levels have been found in many lysosomal storage diseases (LSDs), suggesting an association with lysosomal storage material. The gangliosidoses are a group of neurodegenerative LSDs involving the accumulation of either GM1 or GM2 gangliosides resulting from inherited deficiencies in β-galactosidase or β-hexosaminidase, respectively. Little information is available on BMP levels in gangliosidosis brain tissue. Our results showed that the content of BMP in brain was significantly greater in humans and in animals (mice, cats, American black bears) with either GM1 or GM2 ganglioside storage diseases, than in brains of normal subjects. The storage of BMP and ganglioside GM2 in brain were reduced similarly following adeno-associated viral-mediated gene therapy in Sandhoff disease mice. We also found that C22:6, C18:0, and C18:1 were the predominant BMP fatty acid species in gangliosidosis brains. The results show that BMP accumulates as a secondary storage material in the brain of a broad range of mammals with gangliosidoses.
authors: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors: Zeynep
authors: Z
authors: Akgoc
authors: Department of Neurology and Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605.
authors: Miguel
authors: M
authors: Sena-Esteves
authors: Scott-Ritchey Research Center and Department of Anatomy, Physiology, and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL 36849.
authors: Douglas R
authors: DR
authors: Martin
authors: Sanford-Burnham Medical Research Institute, Orlando, FL 32827.
authors: Xianlin
authors: X
authors: Han
authors: St. Jude Children's Research Hospital, Memphis, TN 38105.
authors: Alessandra
authors: A
authors: d'Azzo
authors: Department of Biology, Boston College, Chestnut Hill, MA 02467.
authors: Thomas N
authors: TN
authors: Seyfried
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002371:Cat Diseases / Q000378:metabolism*; D002415:Cats; D005260:Female; D016537:Gangliosidosis, GM1 / Q000378:metabolism / Q000662:veterinary*; D006801:Humans; D050356:Lipid Metabolism; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D050178:Monoglycerides / Q000378:metabolism*; D012497:Sandhoff Disease / Q000378:metabolism / Q000662:veterinary*; D001503:Ursidae
chemical_list: D008246:Lysophospholipids; D050178:Monoglycerides; C012786:bis(monoacylglyceryl)phosphate
keywords: GM1-gangliosidosis; Sandhoff disease; brain lipids; fatty acid; gangliosides; gene therapy; lysosomal; phospholipids; storage diseases