title: Testing synthetic amyloid-β aggregation inhibitor using single molecule atomic force spectroscopy.
abstract: Alzheimer's disease is a neurodegenerative disease with no known cure and few effective treatment options. The principal neurotoxic agent is an oligomeric form of the amyloid-β peptide and one of the treatment options currently being studied is the inhibition of amyloid aggregation. In this work, we test a novel pseudopeptidic aggregation inhibitor designated as SG1. SG1 has been designed to bind at the amyloid-β self-recognition site and prevent amyloid-β from misfolding into β sheet. We used atomic force spectroscopy, a nanoscale measurement technique, to quantify the binding forces between two single amyloid peptide molecules. For the first time, we demonstrate that single molecule atomic force spectroscopy can be used to assess the effectiveness of amyloid aggregation inhibitors by measuring the experimental yield of binding and can potentially be used as a screening technique for quick testing of efficacy of inhibitor drugs for amyloid aggregation.
authors: University of Waterloo, Department of Biology, 200 University Ave. West, Waterloo, Ontario, Canada N2L 3G1.
authors: Francis T
authors: FT
authors: Hane
authors: University of Waterloo, Department of Biology, 200 University Ave. West, Waterloo, Ontario, Canada N2L 3G1.
authors: Brenda Y
authors: BY
authors: Lee
authors: University of Calgary, Department of Chemistry, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
authors: Anahit
authors: A
authors: Petoyan
authors: University of Calgary, Department of Chemistry, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
authors: Arvi
authors: A
authors: Rauk
authors: University of Waterloo, Department of Biology, 200 University Ave. West, Waterloo, Ontario, Canada N2L 3G1; University of Waterloo, Department of Physics and Astronomy, 200 University Ave. West, Waterloo, Ontario, Canada N2L 3G1. Electronic address: zleonenk@uwaterloo.ca.
authors: Zoya
authors: Z
authors: Leonenko
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000648:ultrastructure; D015374:Biosensing Techniques / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D018625:Microscopy, Atomic Force / Q000379:methods; D056004:Molecular Dynamics Simulation
chemical_list: D016229:Amyloid beta-Peptides
keywords: Aggregation inhibitor; Alzheimer's disease; Amyloid-β aggregation; Fibril formation; Molecular dynamics simulations; Single molecule force spectroscopy