TY  - JOUR
AU  - Zhang, Tao
AU  - Pauly, Thomas
AU  - Nagel-Steger, Luitgard
TI  - Stoichiometric Zn 2+ interferes with the self-association of Aβ42: Insights from size distribution analysis
JO  - International journal of biological macromolecules
VL  - 113
SN  - 0141-8130
CY  - New York, NY [u.a.]
PB  - Elsevier
M1  - FZJ-2018-01403
SP  - 631-639
PY  - 2018
AB  - The abnormal aggregation of amyloid β (Aβ) peptides in the brain has been recognized as a central event in Alzheimer's disease (AD). Divalent metal ions such as Zn2+ have been shown to be closely involved in modulating Aβ self-association. Although the link between Zn2+ dyshomeostasis and brain Aβ deposition has been established, the effect of Zn2+ on the aggregation of Aβ is still incompletely clarified. By combining analytical ultracentrifugation (AUC), circular dichroism (CD) spectroscopy, thioflavin T (ThT) assay and atomic force microscopy (AFM) imaging, we analyzed the impact of stoichiometric Zn2+ on the aggregation process of Aβ42, the main toxic isoform of Aβ species in the brain. Aβ42 aggregates found in the presence of Zn2+ were smaller in size, non-fibrillary and showed less β-sheet structures than aggregates formed in absence of Zn2+. AUC showed that Zn2+ was capable of retaining monomeric Aβ42 in solution. Zn2+ chelation by EDTA totally reversed the inhibitory effect of Zn2+ on Aβ42 fibrillation. Our results provide further evidence that Zn2+ shifts the self-association of Aβ42 toward a non-fibrillary pathway by interfering with the aggregation process at multiple levels.
LB  - PUB:(DE-HGF)16
C6  - pmid:29476859
UR  - <Go to ISI:>//WOS:000432503100074
DO  - DOI:10.1016/j.ijbiomac.2018.02.123
UR  - https://juser.fz-juelich.de/record/843873
ER  -