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

Zeynep Akgoc, Miguel Sena-Esteves, Douglas R. Martin, Xianlin Han, Alessandra D'Azzo, Thomas N. Seyfried

Research output: Contribution to journalArticle

18 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1006-1013
Number of pages8
JournalJournal of Lipid Research
Volume56
Issue number5
DOIs
StatePublished - May 1 2015
Externally publishedYes

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Keywords

  • Fatty acid
  • Gangliosides
  • Gene therapy
  • GM1-gangliosidosis
  • Lysosomal
  • Phospholipids
  • Sandhoff disease
  • Storage diseases
  • Supplementary brain lipids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Akgoc, Z., Sena-Esteves, M., Martin, D. R., Han, X., D'Azzo, A., & Seyfried, T. N. (2015). Bis(monoacylglycero)phosphate: A secondary storage lipid in the gangliosidoses. Journal of Lipid Research, 56(5), 1006-1013. https://doi.org/10.1194/jlr.M057851