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Morphology-specific inhibition of β-amyloid aggregates by 17β-hydroxysteroid dehydrogenase type 10

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Abstract

A major hallmark of Alzheimer's disease (AD) is the formation of toxic aggregates composed of the β-amyloid peptide (Aβ). Given that Aβ peptides are known to co-localize within mitochondria and interact with 17β-HSD10, a mitochondrial protein expressed at high levels in AD brains, we have investigated the inhibitory potential of 17β-HSD10 against Aβ aggregation across a range of physiological conditions. The fluorescence self-quenching (FSQ) of Aβ(1-42), labelled with HiLyte Fluor 555, was used as a sensing strategy to evaluate the inhibitory effect of 17β-HSD10 under well-established conditions to grow distinct Aβ morphologies. Our results indicate that 17β-HSD10 preferentially inhibits the formation of globular and fibrillar-like structures but has no effect on the growth of amorphous plaque-like aggregates at endosomal pH 6. This work provides insights into the dependence of the Aβ-17β-HSD10 interaction with the morphology of Aβ aggregates and how this impacts enzymatic function.
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Original languageEnglish
Pages (from-to)1029-1037
JournalChemBioChem
Volume17
Issue number11
Early online date25 Apr 2016
DOIs
StatePublished - 2 Jun 2016

    Research areas

  • β-Amyloid peptide, 17β-hydroxysteroid dehydrogenase type 10, Alzheimer's disease, Fluorescence self-quenching, neurochemistry

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