title: Secondary alterations of sphingolipid metabolism in lysosomal storage diseases.
abstract: In several neurodegenerative diseases, sphingolipid metabolism is deeply deregulated, leading to the expression of abnormal membrane sphingolipid patterns and altered plasma membrane organization. In this paper, we review the potential importance of these alterations to the pathogenesis of these diseases and focus the reader's attention on some secondary alterations of sphingolipid metabolism that have been sporadically reported in the literature. Moreover, we present a detailed analysis of the lipid composition of different central nervous system and extraneural tissues from the acid sphingomyelinase-deficient mouse, the animal model for Niemann-Pick disease type A, characterized by the accumulation of sphingomyelin. Our data show an unexpected, tissue specific selection of the accumulated molecular species of sphingomyelin, and an accumulation of GM3 and GM2 gangliosides in both neural and extraneural tissues, that cannot be solely explained by the lack of acid sphingomyelinase.
authors.affiliation: Department of Medical Chemistry, Biochemistry and Biotechnology, Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Fratelli Cervi 93, 20090 Segrate, Italy. alessandro.prinetti@unimi.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Prinetti
authors.forename: Simona
authors.initials: S
authors.lastname: Prioni
authors.forename: Elena
authors.initials: E
authors.lastname: Chiricozzi
authors.forename: Edward H
authors.initials: EH
authors.lastname: Schuchman
authors.forename: Vanna
authors.initials: V
authors.lastname: Chigorno
authors.forename: Sandro
authors.initials: S
authors.lastname: Sonnino
mesh_terms: D000818:Animals; D005732:Gangliosides / Q000378:metabolism; D016695:Glycosyltransferases / Q000378:metabolism; D050356:Lipid Metabolism; D016464:Lysosomal Storage Diseases / Q000378:metabolism* / Q000473:pathology; D009420:Nervous System / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000473:pathology; D009542:Niemann-Pick Diseases / Q000378:metabolism / Q000473:pathology; D013107:Sphingolipids / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D005732:Gangliosides; D013107:Sphingolipids; D016695:Glycosyltransferases