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

Aitken, L., Quinn, S. D. , Perez-Gonzalez, C., Samuel, I. D. W., Penedo, J. C. and Gunn-Moore, F. J. (2016) Morphology-specific inhibition of β-amyloid aggregates by 17β-hydroxysteroid dehydrogenase type 10. ChemBioChem, 17(11), pp. 1029-1037. (doi:10.1002/cbic.201600081) (PMID:26991863)

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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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Quinn, Dr Steven
Authors: Aitken, L., Quinn, S. D., Perez-Gonzalez, C., Samuel, I. D. W., Penedo, J. C., and Gunn-Moore, F. J.
College/School:College of Science and Engineering > School of Chemistry
Journal Name:ChemBioChem
Publisher:Wiley-VCH Verlag
ISSN:1439-4227
ISSN (Online):1439-7633
Published Online:25 April 2016
Copyright Holders:Copyright © 2016 Wiley-VCH Verlag
First Published:First published in ChemBioChem 17(11):1029-1037
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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