Zn2+-Aβ40 complexes form metastable quasi-spherical oligomers that are cytotoxic to cultured hippocampal neurons

Inna Solomonov, Eduard Korkotian, Benjamin Born, Yishay Feldman, Arkady Bitler, Farid Rahimi, Huiyuan Li, Gal Bitan, Irit Sagi

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

The roles of metal ions in promoting amyloid β-protein (Aβ) oligomerization associated with Alzheimer disease are increasingly recognized. However, the detailed structures dictating toxicity remain elusive for Aβ oligomers stabilized by metal ions. Here, we show that small Zn 2+-bound Aβ1-40 (Zn2+- Aβ40) oligomers formed in cell culture medium exhibit quasispherical structures similar to native amylospheroids isolated recently from Alzheimer disease patients. These quasi-spherical Zn2+-Aβ40 oligomers irreversibly inhibit spontaneous neuronal activity and cause massive cell death in primary hippocampal neurons. Spectroscopic and x-ray diffraction structural analyses indicate that despite their non-fibrillar morphology, the metastable Zn 2+-Aβ40 oligomers are rich in β-sheet and cross-β structures. Thus, Zn2+ promotes Aβ40 neurotoxicity by structural organization mechanisms mediated by coordination chemistry.

Original languageEnglish
Pages (from-to)20555-20564
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number24
DOIs
StatePublished - 8 Jun 2012
Externally publishedYes

Funding

FundersFunder number
National Institute on AgingP01AG027818
National Cancer InstituteR01CA098799

    Fingerprint

    Dive into the research topics of 'Zn2+-Aβ40 complexes form metastable quasi-spherical oligomers that are cytotoxic to cultured hippocampal neurons'. Together they form a unique fingerprint.

    Cite this