title: Deregulated sphingolipid metabolism and membrane organization in neurodegenerative disorders.
abstract: Sphingolipids are polar membrane lipids present as minor components in eukaryotic cell membranes. Sphingolipids are highly enriched in nervous cells, where they exert important biological functions. They deeply affect the structural and geometrical properties and the lateral order of cellular membranes, modulate the function of several membrane-associated proteins, and give rise to important intra- and extracellular lipid mediators. Sphingolipid metabolism is regulated along the differentiation and development of the nervous system, and the expression of a peculiar spatially and temporarily regulated sphingolipid pattern is essential for the maintenance of the functional integrity of the nervous system: sphingolipids in the nervous system participate to several signaling pathways controlling neuronal survival, migration, and differentiation, responsiveness to trophic factors, synaptic stability and synaptic transmission, and neuron-glia interactions, including the formation and stability of central and peripheral myelin. In several neurodegenerative diseases, sphingolipid metabolism is deeply deregulated, leading to the expression of abnormal sphingolipid patterns and altered membrane organization that participate to several events related to the pathogenesis of these diseases. The most impressive consequence of this deregulation is represented by anomalous sphingolipid-protein interactions that are at least, in part, responsible for the misfolding events that cause the fibrillogenic and amyloidogenic processing of disease-specific protein isoforms, such as amyloid beta peptide in Alzheimer's disease, huntingtin in Huntington's disease, alpha-synuclein in Parkinson's disease, and prions in transmissible encephalopathies. Targeting sphingolipid metabolism represents today an underexploited but realistic opportunity to design novel therapeutic strategies for the intervention in these diseases.
authors.affiliation: Section of Biochemistry, Department of Medicine and Experimental Oncology, University of Turin, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Piccinini
authors.forename: Federica
authors.initials: F
authors.lastname: Scandroglio
authors.forename: Simona
authors.initials: S
authors.lastname: Prioni
authors.forename: Barbara
authors.initials: B
authors.lastname: Buccinnà
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Loberto
authors.forename: Massimo
authors.initials: M
authors.lastname: Aureli
authors.forename: Vanna
authors.initials: V
authors.lastname: Chigorno
authors.forename: Elisa
authors.initials: E
authors.lastname: Lupino
authors.forename: Giovanni
authors.initials: G
authors.lastname: DeMarco
authors.forename: Annarosa
authors.initials: A
authors.lastname: Lomartire
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rinaudo
authors.forename: Sandro
authors.initials: S
authors.lastname: Sonnino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Prinetti
mesh_terms: D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009186:Myelin Sheath / Q000737:chemistry / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000473:pathology / Q000503:physiopathology*; D017096:Prion Diseases / Q000473:pathology / Q000503:physiopathology; D013106:Sphingolipidoses / Q000473:pathology / Q000503:physiopathology; D013107:Sphingolipids / Q000737:chemistry / Q000378:metabolism*
chemical_list: D013107:Sphingolipids