Journal Article

FZJ-2018-05747

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Inhibition of amyloid Aβ aggregation by high pressures or specific D-enantiomeric peptides

Cavini, I. A. ; Munte, C. E. ; Erlach, M. B. ; van Groen, T. ; Kadish, I. ; Zhang, T.FZJ* ; Ziehm, T.FZJ* ; Nagel-Steger, L.FZJ* ; Kutzsche, J.FZJ* ; Kremer, W. ; Willbold, D.FZJ* ; Kalbitzer, H. R. (Corresponding author)

2018
Soc. Cambridge

This record in other databases:      

Please use a persistent id in citations: doi:10.1039/C8CC01458B

Abstract: Pressure can shift the polymer–monomer equilibrium of Aβ, increasing pressure first leads to a release of Aβ-monomers, surprisingly at pressures higher than 180 MPa repolymerization is induced. By high pressure NMR spectroscopy, differences of partial molar volumes ΔV0 and compressibility factors Δβ′ of polymerization were determined at different temperatures. The D-enantiomeric peptides RD2 and RD2D3 bind to monomeric Aβ with affinities substantially higher than those determined for fibril formation. By reducing the Aβ 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 Aβ alone indicating the recognition of a more compact conformation of Aβ identified by high pressure NMR before.

---

Contributing Institute(s):

1. Strukturbiochemie (ICS-6)

Research Program(s):

1. 553 - Physical Basis of Diseases (POF3-553) (POF3-553)

Appears in the scientific report 2018

---

Database coverage:
; Allianz-Lizenz / DFG ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; National-Konsortium ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection

---