Susceptibility of amyloid β peptide degrading enzymes to oxidative damage: A potential Alzheimer's disease spiral

Heather Shinall, Eun Suk Song, Louis B. Hersh

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

Abstract

Insulysin (IDE) and neprilysin (NEP) were found to be inactivated by oxidation with hydrogen peroxide, an iron-ascorbate oxidation system, and by treatment with 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH). In each case reaction led to the introduction of protein carbonyl groups as judged by reaction with 2,4-dintrophenylhydrazine. IDE was inactivated by reaction with 4-hydroxy-2-nonenal (HNE) with the concomitant formation of protein adducts. NEP was not inactivated to a significant extent by HNE, but some HNE-adduct formation did occur. Prior reaction with hydrogen peroxide or AAPH led to enhanced formation of HNE adducts. Treatment of IDE with AAHP or hydrogen peroxide increased its susceptibility to proteolysis, while treatment of NEP with iron/ascorbate or hydrogen peroxide increased its susceptibility to proteolysis. Since IDE and NEP play a prominent role in the clearance of amyloid β peptides, their oxidative inactivation and enhanced proteolysis can contribute to the onset and/or progression of Alzheimer's disease.

Original languageEnglish
Pages (from-to)15345-15350
Number of pages6
JournalBiochemistry
Volume44
Issue number46
DOIs
StatePublished - Nov 22 2005

ASJC Scopus subject areas

  • Biochemistry

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