Journal article

Amyloid-Beta Peptide Aβ3pE-42 Induces Lipid Peroxidation, Membrane Permeabilization and Calcium-Influx in Neurons

A BUSH, AP Gunn, BX Wong, T Johanssen, JC Griffith, CL Masters, KJ Barnham, JA Duce, RA Cherny

Journal of Biological Chemistry | American Society for Biochemistry and Molecular Biology | Published : 2016

Abstract

Pyroglutamate-modified amyloid-β (pE-Aβ) is a highly neurotoxic amyloid-β (Aβ) isoform and is enriched in the brains of individuals with Alzheimer disease compared with healthy aged controls. Pyroglutamate formation increases the rate of Aβ oligomerization and alters the interactions of Aβ with Cu(2+) and lipids; however, a link between these properties and the toxicity of pE-Aβ peptides has not been established. We report here that Aβ3pE-42 has an enhanced capacity to cause lipid peroxidation in primary cortical mouse neurons compared with the full-length isoform (Aβ(1-42)). In contrast, Aβ(1-42) caused a significant elevation in cytosolic reactive oxygen species, whereas Aβ3pE-42 did not. ..

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Grants

Awarded by National Health and Medical Research Council (NHMRC) of Australia


Awarded by Senior Research Fellowship


Awarded by Australia Fellowship


Awarded by Alzheimers Research UK


Funding Acknowledgements

This work was supported by National Health and Medical Research Council (NHMRC) of Australia Program Grant 628946 (to R. A. C., K. J. B., A. I. B., and C. L. M.), Senior Research Fellowship APP1002373 (to K. J. B.), Australia Fellowship GNT1037234 (to A. I. B.), and Operational Infrastructure Support Grant from the Victorian Government (to Florey Institute of Neuroscience and Mental Health). The authors declare that they have no conflicts of interest with the contents of this article.