title: Multi-system disorders of glycosphingolipid and ganglioside metabolism.
abstract: Glycosphingolipids (GSLs) and gangliosides are a group of bioactive glycolipids that include cerebrosides, globosides, and gangliosides. These lipids play major roles in signal transduction, cell adhesion, modulating growth factor/hormone receptor, antigen recognition, and protein trafficking. Specific genetic defects in lysosomal hydrolases disrupt normal GSL and ganglioside metabolism leading to their excess accumulation in cellular compartments, particularly in the lysosome, i.e., lysosomal storage diseases (LSDs). The storage diseases of GSLs and gangliosides affect all organ systems, but the central nervous system (CNS) is primarily involved in many. Current treatments can attenuate the visceral disease, but the management of CNS involvement remains an unmet medical need. Early interventions that alter the CNS disease have shown promise in delaying neurologic involvement in several CNS LSDs. Consequently, effective treatment for such devastating inherited diseases requires an understanding of the early developmental and pathological mechanisms of GSL and ganglioside flux (synthesis and degradation) that underlie the CNS diseases. These are the focus of this review.
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
authors.forename: You-Hai
authors.initials: YH
authors.lastname: Xu
authors.forename: Sonya
authors.initials: S
authors.lastname: Barnes
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Grabowski
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism / Q000502:physiology; D005732:Gangliosides / Q000737:chemistry / Q000378:metabolism*; D006028:Glycosphingolipids / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D016464:Lysosomal Storage Diseases / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D015394:Molecular Structure; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology
chemical_list: D005732:Gangliosides; D006028:Glycosphingolipids