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J Inorg Biochem. 2017 Sep;174:130-136. doi: 10.1016/j.jinorgbio.2017.06.007. Epub 2017 Jun 20.

Covalent modifications of the amyloid beta peptide by hydroxynonenal: Effects on metal ion binding by monomers and insights into the fibril topology.

Author information

1
Department of Chemical Sciences, University of Catania, Viale A., Doria 6, 95125, Catania, Italy. Electronic address: grassog@unict.it.
2
Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
3
Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Electronic address: axe@pharm.med.upenn.edu.

Abstract

Amyloid β peptides (Aβ) and metal ions are associated with oxidative stress in Alzheimer's disease (AD). Oxidative stress, acting on ω-6 polyunsaturated fatty acyl chains, produces diverse products, including 4-hydroxy-2-nonenal (HNE), which can covalently modify the Aβ that helped to produce it. To examine possible feedback mechanisms involving Aβ, metal ions and HNE production, the effects of HNE modification and fibril formation on metal ion binding was investigated. Results indicate that copper(II) generally inhibits the modification of His side chains in Aβ by HNE, but that once modified, copper(II) still binds to Aβ with high affinity. Fibril formation protects only one of the three His residues in Aβ from HNE modification, and this protection is consistent with proposed models of fibril structure. These results provide insight into a network of biochemical reactions that may be operating as a consequence of oxidative stress in AD, or as part of the pathogenic process.

PMID:
28668508
DOI:
10.1016/j.jinorgbio.2017.06.007
[Indexed for MEDLINE]

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