Morphology-Specific Inhibition of β-Amyloid Aggregates by 17β-Hydroxysteroid Dehydrogenase Type 10

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. 17 β-HSD10 interaction with Aβ amyloid: what type of amyloid? 17β-hydroxysteroid dehydrogenase type 10 interacts with β-amyloid (Aβ) aggregates and suppresses Aβ-induced apoptosis in neurons, but the aggregate morphology inhibited by 17β-HSD10 remains unknown. Fluorescence self-quenching demonstrated that fibrils and globular aggregates, but not plaques, are targeted by 17β-HSD10.