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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibition of amyloid Ab aggregation by high pressures or specific D-enantiomeric peptides

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Author(s):
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Cavini, Italo A. [1, 2] ; Munte, Claudia E. [1, 2] ; Erlach, Markus Beck [2] ; van Groen, Thomas [3] ; Kadish, Inga [3] ; Zhang, Tao [4, 5] ; Ziehm, Tamar [5] ; Nagel-Steger, Luitgard [4, 5] ; Kutzsche, Janine [5] ; Kremer, Werner [2] ; Willbold, Dieter [4, 5] ; Kalbitzer, Hans Robert [2]
Total Authors: 12
Affiliation:
[1] Univ Sao Paulo, Phys Inst Sao Carlos, Sao Carlos, SP - Brazil
[2] Univ Regensburg, Inst Biophys & Phys Biochem, Univ Str 31, D-93053 Regensburg - Germany
[3] Univ Alabama Birmingham, Birmingham, AL 35294 - USA
[4] Heinrich Heine Univ Dusseldorf, Inst Phys Biol & BMFZ, D-40225 Dusseldorf - Germany
[5] Forschungszentrum Julich, Struct Biochem ICS 6, Inst Complex Syst, D-52425 Julich - Germany
Total Affiliations: 5
Document type: Journal article
Source: CHEMICAL COMMUNICATIONS; v. 54, n. 26, p. 3294-3297, APR 4 2018.
Web of Science Citations: 7
Abstract

Pressure can shift the polymer-monomer equilibrium of A beta, increasing pressure first leads to a release of A beta-monomers, surprisingly at pressures higher than 180 MPa repolymerization is induced. By high pressure NMR spectroscopy, differences of partial molar volumes Delta V-0 and compressibility factors Delta beta' of polymerization were determined at different temperatures. The D-enantiomeric peptides RD2 and RD2D3 bind to monomeric A beta with affinities substantially higher than those determined for fibril formation. By reducing the A beta concentration below the critical concentration for polymerization they inhibit the formation of toxic oligomers. Chemical shift perturbation allows the identification of the binding sites. The D-peptides are candidates for drugs preventing Alzheimer's disease. We show that RD2D3 has a positive effect on the cognitive behaviour of transgenic (APPSwDI) mice prone to Alzheimer's disease. The heterodimer complexes have a smaller Stokes radius than A beta alone indicating the recognition of a more compact conformation of A beta identified by high pressure NMR before. (AU)

FAPESP's process: 10/01362-5 - Interaction of proteins with lipidic microdomains and biological membrane models
Grantee:Claudia Elisabeth Munte
Support type: Regular Research Grants
FAPESP's process: 13/04433-9 - Structure and dynamics of excited rare states of the Alzheimer's disease beta-amyloid peptide studied by high-pressure NMR
Grantee:Italo Augusto Cavini
Support type: Scholarships in Brazil - Doctorate (Direct)