Lyso-glycosphingolipids: presence and consequences

Essays Biochem. 2020 Sep 23;64(3):565-578. doi: 10.1042/EBC20190090.

Abstract

Lyso-glycosphingolipids are generated in excess in glycosphingolipid storage disorders. In the course of these pathologies glycosylated sphingolipid species accumulate within lysosomes due to flaws in the respective lipid degrading machinery. Deacylation of accumulating glycosphingolipids drives the formation of lyso-glycosphingolipids. In lysosomal storage diseases such as Gaucher Disease, Fabry Disease, Krabbe disease, GM1 -and GM2 gangliosidosis, Niemann Pick type C and Metachromatic leukodystrophy massive intra-lysosomal glycosphingolipid accumulation occurs. The lysosomal enzyme acid ceramidase generates the deacylated lyso-glycosphingolipid species. This review discusses how the various lyso-glycosphingolipids are synthesized, how they may contribute to abnormal immunity in glycosphingolipid storing lysosomal diseases and what therapeutic opportunities exist.

Keywords: acid ceramidase; glycosphingolipid; immune response; lysosomal storage disease.

Publication types

  • Review

MeSH terms

  • Acid Ceramidase / metabolism
  • Animals
  • Enzyme Replacement Therapy / methods*
  • Genetic Therapy / methods*
  • Glycosphingolipids / biosynthesis*
  • Humans
  • Immunity
  • Lysosomal Storage Diseases / drug therapy*
  • Lysosomal Storage Diseases / immunology
  • Lysosomal Storage Diseases / metabolism*
  • Lysosomes / metabolism*
  • Molecular Targeted Therapy / methods*

Substances

  • Glycosphingolipids
  • Acid Ceramidase