TY  - JOUR
A1  - Lieblein, Tobias
A1  - Zangl, Rene
A1  - Martin, Janosch
A1  - Hoffmann, Jan
A1  - Hutchison, Marie J.
A1  - Stark, Tina
A1  - Stirnal, Elke
A1  - Schrader, Thomas
A1  - Schwalbe, Harald
A1  - Morgner, Nina
T1  - Structural rearrangement of amyloid-β upon inhibitor binding suppresses formation of Alzheimer's disease related oligomers
T2  - eLife
N2  - The formation of oligomers of the amyloid-β peptide plays a key role in the onset of Alzheimer's disease. We describe herein the investigation of disease-relevant small amyloid-β oligomers by mass spectrometry and ion mobility spectrometry, revealing functionally relevant structural attributes. In particular, we can show that amyloid-β oligomers develop in two distinct arrangements leading to either neurotoxic oligomers and fibrils or non-toxic amorphous aggregates. Comprehending the key-attributes responsible for those pathways on a molecular level is a pre-requisite to specifically target the peptide's tertiary structure with the aim to promote the emergence of non-toxic aggregates. Here, we show for two fibril inhibiting ligands, an ionic molecular tweezer and a hydrophobic peptide that despite their different interaction mechanisms, the suppression of the fibril pathway can be deduced from the disappearance of the corresponding structure of the first amyloid-β oligomers.
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/62363
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-623636
SN  - 2050-084X
VL  - 9
IS  - art. e59306
SP  - 1
EP  - 27
PB  - eLife Sciences Publications
CY  - Cambridge
ER  -