title: Amyloid Fibres: Inert End-Stage Aggregates or Key Players in Disease?
abstract: The formation of amyloid fibres is a hallmark of amyloid disorders. Nevertheless, the lack of correlation between fibre load and disease as observed, for example, in Alzheimer's disease, means that fibres are considered secondary contributors to the onset of cellular dysfunction. Instead, soluble intermediates of amyloid assembly are often described as the agents of toxicity. Here, we discuss recent experimental discoveries which suggest that amyloid fibres should be considered as disease-relevant species that can mediate a range of pathological processes. These include disruption of biological membranes, secondary nucleation, amyloid aggregate transmission, and the disruption of protein homeostasis (proteostasis). Thus, a greater understanding of amyloid fibre biology could enhance prospects of developing therapeutic interventions against this devastating class of protein-misfolding disorders.
authors.affiliation: Astbury Centre for Structural Molecular Biology and School of Molecular and Cellular Biology, The University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Tipping
authors.affiliation: Astbury Centre for Structural Molecular Biology and School of Molecular and Cellular Biology, The University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Patricija
authors.initials: P
authors.lastname: van Oosten-Hawle
authors.affiliation: Astbury Centre for Structural Molecular Biology and School of Molecular and Cellular Biology, The University of Leeds, Leeds, LS2 9JT, UK.
authors.forename: Eric W
authors.initials: EW
authors.lastname: Hewitt
authors.affiliation: Astbury Centre for Structural Molecular Biology and School of Molecular and Cellular Biology, The University of Leeds, Leeds, LS2 9JT, UK. Electronic address: s.e.radford@leeds.ac.uk.
authors.forename: Sheena E
authors.initials: SE
authors.lastname: Radford
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism*; D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D006801:Humans; D066263:Protein Aggregation, Pathological; D057165:Proteostasis Deficiencies / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D000682:Amyloid
keywords: amyloid; disease; fibres; transmission