title: How is protein aggregation in amyloidogenic diseases modulated by biological membranes?
abstract: The fate of proteins with amyloidogenic properties depends critically on their immediate biochemical environment. However, the role of biological interfaces such as membrane surfaces, as promoters of pathological aggregation of amyloidogenic proteins, is rarely studied and only established for the amyloid-beta protein (A beta) involved in Alzheimer's disease, and alpha-synuclein in Parkinsonism. The occurrence of binding and misfolding of these proteins on membrane surfaces, is poorly understood, not at least due to the two-dimensional character of this event. Clearly, the nature of the folding pathway for A beta protein adsorbed upon two-dimensional aggregation templates, must be fundamentally different from the three-dimensional situation in solution. Here, we summarize the current research and focus on the function of membrane interfaces as aggregation templates for amyloidogenic proteins (and even prionic ones). One major aspect will be the relationship between membrane properties and protein association and the consequences for amyloidogenic products. The other focus will be on a general understanding of protein folding pathways on two-dimensional templates on a molecular level. Finally, we will demonstrate the potential importance of membrane-mediated aggregation for non-amphiphatic soluble amyloidogenic proteins, by using the SOD1 protein involved in the amyotrophic lateral sclerosis syndrome.
authors.affiliation: Department of Chemistry, Umeå University, 90187 Umeå, Sweden.
authors.forename: Christopher
authors.initials: C
authors.lastname: Aisenbrey
authors.forename: Tomasz
authors.initials: T
authors.lastname: Borowik
authors.forename: Roberth
authors.initials: R
authors.lastname: Byström
authors.forename: Marcus
authors.initials: M
authors.lastname: Bokvist
authors.forename: Fredrick
authors.initials: F
authors.lastname: Lindström
authors.forename: Hanna
authors.initials: H
authors.lastname: Misiak
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Sani
authors.forename: Gerhard
authors.initials: G
authors.lastname: Gröbner
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry* / Q000473:pathology*; D019281:Dimerization; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000503:physiopathology*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D012995:Solubility; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013499:Surface Properties; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D046912:Multiprotein Complexes; C000606290:SOD1 protein, human; D051844:alpha-Synuclein; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1