title: Glycosphingolipid depletion in PC12 cells using iminosugars protects neuronal membranes from anti-ganglioside antibody mediated injury.
abstract: Autoimmune neuropathies are frequently associated with pathogenic anti-ganglioside antibodies targeting ganglioside-rich neuronal and glial membranes. The extent of injury is determined by the concentration of membrane ganglioside and thus reduction might be expected to attenuate disease. In this study, we suppressed ganglioside biosynthesis in PC12 cells with the glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin and observed reduced plasma membrane antibody binding and a major neuroprotective effect in complement-mediated lysis assays. These data demonstrate that iminosugar inhibitors, currently used to treat type 1 Gaucher disease, are also of potential value for depleting antigen and thereby suppressing tissue injury in anti-ganglioside antibody-associated neuropathy.
authors.affiliation: Division of Clinical Neurosciences, Glasgow Biomedical Research Centre, University of Glasgow, Scotland G12 8TA, United Kingdom.
authors.forename: Kate H
authors.initials: KH
authors.lastname: Townson
authors.forename: Anneliese O
authors.initials: AO
authors.lastname: Speak
authors.forename: Kay N
authors.initials: KN
authors.lastname: Greenshields
authors.forename: Carl S
authors.initials: CS
authors.lastname: Goodyear
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Willison
authors.forename: Frances M
authors.initials: FM
authors.lastname: Platt
mesh_terms: D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003165:Complement System Proteins / Q000276:immunology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005732:Gangliosides / Q000276:immunology* / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism*; D050111:Imino Sugars / Q000378:metabolism; D009444:Neuritis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D051381:Rats
chemical_list: D000906:Antibodies; D004791:Enzyme Inhibitors; D005732:Gangliosides; D006028:Glycosphingolipids; D050111:Imino Sugars; D018696:Neuroprotective Agents; D017485:1-Deoxynojirimycin; C016481:trisialoganglioside GT1; D003165:Complement System Proteins; C059896:miglustat