title: The relationship between amyloid structure and cytotoxicity.
abstract: Self-assembly of proteins and peptides into amyloid structures has been the subject of intense and focused research due to their association with neurodegenerative, age-related human diseases and transmissible prion diseases in humans and mammals. Of the disease associated amyloid assemblies, a diverse array of species, ranging from small oligomeric assembly intermediates to fibrillar structures, have been shown to have toxic potential. Equally, a range of species formed by the same disease associated amyloid sequences have been found to be relatively benign under comparable monomer equivalent concentrations and conditions. In recent years, an increasing number of functional amyloids have also been found. These developments show that not all amyloid structures are generically toxic to cells. Given these observations, it is important to understand why amyloid structures may encode such varied toxic potential despite sharing a common core molecular architecture. Here, we discuss possible links between different aspects of amyloidogenic structures and assembly mechanisms with their varied functional effects. We propose testable hypotheses for the relationship between amyloid structure and its toxic potential in the context of recent reports on amyloid sequence, structure, and toxicity relationships.
authors.affiliation: School of Life Sciences; University of Sussex; Falmer, East Sussex UK; School of Biological Sciences; University of Kent; Canterbury, Kent UK.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Marshall
authors.affiliation: School of Life Sciences; University of Sussex; Falmer, East Sussex UK; School of Biological Sciences; University of Kent; Canterbury, Kent UK.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Marchante
authors.affiliation: School of Life Sciences; University of Sussex; Falmer, East Sussex UK; School of Biological Sciences; University of Kent; Canterbury, Kent UK.
authors.forename: Wei-Feng
authors.initials: WF
authors.lastname: Xue
authors.affiliation: School of Life Sciences; University of Sussex; Falmer, East Sussex UK; School of Biological Sciences; University of Kent; Canterbury, Kent UK.
authors.forename: Louise C
authors.initials: LC
authors.lastname: Serpell
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000633:toxicity*; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000682:Amyloid
keywords: Amyloidosis; amyloid; cross-β; cytotoxicity; deposition; fibril; oligomer; structure