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J Lipid Res. 2015 May;56(5):1006-13. doi: 10.1194/jlr.M057851. Epub 2015 Mar 20.

Bis(monoacylglycero)phosphate: a secondary storage lipid in the gangliosidoses.

Author information

1
Department of Biology, Boston College, Chestnut Hill, MA 02467.
2
Department of Neurology and Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA 01605.
3
Scott-Ritchey Research Center and Department of Anatomy, Physiology, and Pharmacology, Auburn University College of Veterinary Medicine, Auburn, AL 36849.
4
Sanford-Burnham Medical Research Institute, Orlando, FL 32827.
5
St. Jude Children's Research Hospital, Memphis, TN 38105.

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.

KEYWORDS:

GM1-gangliosidosis; Sandhoff disease; brain lipids; fatty acid; gangliosides; gene therapy; lysosomal; phospholipids; storage diseases

PMID:
25795792
PMCID:
PMC4409277
DOI:
10.1194/jlr.M057851
[Indexed for MEDLINE]
Free PMC Article

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