title: Superresolution imaging of amyloid fibrils with binding-activated probes.
abstract: Protein misfolding into amyloid-like aggregates underlies many neurodegenerative diseases. Thus, insights into the structure and function of these amyloids will provide valuable information on the pathological mechanisms involved and aid in the design of improved drugs for treating amyloid-based disorders. However, determining the structure of endogenous amyloids at high resolution has been difficult. Here we employ binding-activated localization microscopy (BALM) to acquire superresolution images of α-synuclein amyloid fibrils with unprecedented optical resolution. We propose that BALM imaging can be extended to study the structure of other amyloids, for differential diagnosis of amyloid-related diseases and for discovery of drugs that perturb amyloid structure for therapy.
authors.affiliation: Cell Biology and Biophysics, EMBL Heidelberg, Meyerhofstrasse 1, Heidelberg, Germany. jonas.ries@embl.de.
authors.forename: Jonas
authors.initials: J
authors.lastname: Ries
authors.forename: Vinod
authors.initials: V
authors.lastname: Udayar
authors.forename: Alice
authors.initials: A
authors.lastname: Soragni
authors.forename: Simone
authors.initials: S
authors.lastname: Hornemann
authors.forename: K Peter R
authors.initials: KP
authors.lastname: Nilsson
authors.forename: Roland
authors.initials: R
authors.lastname: Riek
authors.forename: Christoph
authors.initials: C
authors.lastname: Hock
authors.forename: Helge
authors.initials: H
authors.lastname: Ewers
authors.forename: Adriano A
authors.initials: AA
authors.lastname: Aguzzi
authors.forename: Lawrence
authors.initials: L
authors.lastname: Rajendran
mesh_terms: D000085:Acetates; D000682:Amyloid / Q000737:chemistry*; D006801:Humans; D008853:Microscopy / Q000379:methods*; D013876:Thiophenes; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D000085:Acetates; D000682:Amyloid; D013876:Thiophenes; D051844:alpha-Synuclein; C572917:pentamer formyl thiophene acetic acid