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.
Highlights
Bis(monoacylglycero)phosphate (BMP) is a negatively charged glycerophospholipid with an unusual sn-1;sn-1′ structural configuration
BMP accumulation was found in all samples of gangliosidosis brain tissue (Fig. 2, Table 1), showing that BMP accumulates as a secondary storage material in the gangliosidosis brain
BMP comprises a small portion of total phospholipids in normal tissues, BMP levels increase in many lysosomal storage disease (LSD), such as Niemann-Pick, neuronal ceroid lipofuscinoses, mucopolysaccharidosis (MPS I and II), Fabry disease, and Gaucher disease [16, 17, 19,20,21,22,23,24,25]
Summary
Bis(monoacylglycero)phosphate (BMP) is a negatively charged glycerophospholipid with an unusual sn-1;sn-1′ structural configuration. Elevated BMP levels have been found in many lysosomal storage diseases (LSDs), suggesting an association with lysosomal storage material. This reorientation gives BMP its unusual sn-1;sn-1′ structural configuration (based on the phosphate-linked glycerol carbon), which is not observed in other phospholipids [5, 6] (Fig. 1) This unusual configuration is thought to play a role in the resistance of BMP to many phospholipases, and its stability in late endosomes/lysosomes [7, 8]. Elevated levels of BMP are observed in many LSDs, including mucopolysaccharidosis, Niemann-Pick disease type A/B/C, Gaucher disease, and Fabry disease [15,16,17,18,19,20,21,22,23,24,25,26].
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call