title: Morphology-Specific Inhibition of β-Amyloid Aggregates by 17β-Hydroxysteroid Dehydrogenase Type 10.
abstract: A major hallmark of Alzheimer's disease (AD) is the formation of toxic aggregates of the β-amyloid peptide (Aβ). Given that Aβ peptides are known to localise within mitochondria and interact with 17β-HSD10, a mitochondrial protein expressed at high levels in AD brains, we investigated the inhibitory potential of 17β-HSD10 against Aβ aggregation under a range of physiological conditions. Fluorescence self-quenching (FSQ) of Aβ(1-42) labelled with HiLyte Fluor 555 was used to evaluate the inhibitory effect under conditions established to grow distinct Aβ morphologies. 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.
authors.affiliation: School of Biology, University of St. Andrews, Medical and Biological Sciences Building, North Haugh, St. Andrews, Fife, KY16 9TF, UK.
authors.forename: Laura
authors.identifier: 0000-0001-7259-4491
authors.initials: L
authors.lastname: Aitken
authors.affiliation: Organic Semiconductor Centre, SUPA, School of Physics and Astronomy, University of St. Andrews, North Haugh, St. Andrews, Fife, KY16 9SS, UK.|SUPA, School of Physics and Astronomy, University of St. Andrews, North Haugh, St. Andrews, Fife, KY16 9SS, UK.|WestCHEM, School of Chemistry, Joseph Black Building, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK.
authors.forename: Steven D
authors.identifier: 0000-0003-3442-4103
authors.initials: SD
authors.lastname: Quinn
authors.affiliation: SUPA, School of Physics and Astronomy, University of St. Andrews, North Haugh, St. Andrews, Fife, KY16 9SS, UK.|Biomedical Sciences Research Complex, University of St. Andrews, Biomolecular Sciences Building, North Haugh, St. Andrews, Fife, KY16 9ST, UK.
authors.forename: Cibran
authors.identifier: 0000-0003-3202-0711
authors.initials: C
authors.lastname: Perez-Gonzalez
authors.affiliation: Organic Semiconductor Centre, SUPA, School of Physics and Astronomy, University of St. Andrews, North Haugh, St. Andrews, Fife, KY16 9SS, UK.
authors.forename: Ifor D W
authors.initials: ID
authors.lastname: Samuel
authors.affiliation: SUPA, School of Physics and Astronomy, University of St. Andrews, North Haugh, St. Andrews, Fife, KY16 9SS, UK. jcp10@st-andrews.ac.uk.|Biomedical Sciences Research Complex, University of St. Andrews, Biomolecular Sciences Building, North Haugh, St. Andrews, Fife, KY16 9ST, UK. jcp10@st-andrews.ac.uk.
authors.forename: J Carlos
authors.identifier: 0000-0002-5807-5385
authors.initials: JC
authors.lastname: Penedo
authors.affiliation: School of Biology, University of St. Andrews, Medical and Biological Sciences Building, North Haugh, St. Andrews, Fife, KY16 9TF, UK. fjg1@st-andrews.ac.uk.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gunn-Moore
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D009243:NAD / Q000737:chemistry; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D013050:Spectrometry, Fluorescence
chemical_list: D016229:Amyloid beta-Peptides; D005456:Fluorescent Dyes; D010446:Peptide Fragments; D011994:Recombinant Proteins; C075222:amyloid beta-protein (1-42); D009243:NAD; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase
keywords: Alzheimer's disease; amyloid beta-peptides; dehydrogenases; fluorescent probes; neurochemistry