title: Membrane lipid composition and its physicochemical properties define cell vulnerability to aberrant protein oligomers.
abstract: Increasing evidence suggests that the interaction of misfolded protein oligomers with cell membranes is a primary event resulting in the cytotoxicity associated with many protein-misfolding diseases, including neurodegenerative disorders. We describe here the results of a study on the relative contributions to toxicity of the physicochemical properties of protein oligomers and the cell membrane with which they interact. We altered the amount of cholesterol and the ganglioside GM1 in membranes of SH-SY5Y cells. We then exposed the cells to two types of oligomers of the prokaryotic protein HypF-N with different ultrastructural and cytotoxicity properties, and to oligomers formed by the amyloid-β peptide associated with Alzheimer's disease. We identified that the degree of toxicity of the oligomeric species is the result of a complex interplay between the structural and physicochemical features of both the oligomers and the cell membrane.
authors.affiliation: Department of Biochemical Sciences and Research Centre on the Molecular Basis of Neurodegeneration (CIMN), University of Florence, Florence, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Evangelisti
authors.forename: Cristina
authors.initials: C
authors.lastname: Cecchi
authors.forename: Roberta
authors.initials: R
authors.lastname: Cascella
authors.forename: Caterina
authors.initials: C
authors.lastname: Sgromo
authors.forename: Matteo
authors.initials: M
authors.lastname: Becatti
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Dobson
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Chiti
authors.forename: Massimo
authors.initials: M
authors.lastname: Stefani
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism* / Q000633:toxicity; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D055598:Chemical Phenomena; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D008563:Membrane Lipids; D005677:G(M1) Ganglioside; D002784:Cholesterol