Inhibition of the Fibrillation of Amyloid Aβ by Hybrid-Lipid-Polymer Vesicles.

Macromol Biosci

Macromolecular Chemistry, Institute of Chemistry, Faculty of Natural Science II (Chemistry, Physics and Mathematics)Martin Luther University Halle-Wittenberg, von-Danckelmann-Platz 4, D-06120, Halle, Germany.

Published: May 2023

The transformation of functional proteins into amyloidic plaques is responsible for the impairment of neurological functions in patients fallen victim to debilitating neurological conditions like Alzheimer's, Parkinson's, and Huntington's diseases. The nucleating role of amyloid beta (Aβ ) peptide into amyloids is well established. Herein, lipid hybrid-vesicles are generated with glycerol/cholesterol-bearing polymers aiming to alter the nucleation process and modulate the early phases of Aβ fibrillation. Hybrid-vesicles (±100 nm) are prepared by incorporating variable amounts of cholesterol-/glycerol-conjugated poly(di(ethylene glycol) acrylates) polymers into 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membranes. The in vitro fibrillation kinetics coupled to transmission electron microscopy (TEM) is employed to investigate the role of hybrid-vesicles on Aβ fibrillation without destroying the vesicular membrane. Both polymers, when embedded in hybrid-vesicles (up to 20%) significantly prolonged the fibrillation lag phase (t ) compared to a small acceleration in the presence of DOPC vesicles, irrespective of the amount of polymers inside the hybrid-vesicles. Along with this notable retardation effect, a morphological transformation of the amyloid's secondary structures to amorphous aggregates or the absence of fibrillar structures when interacting with the hybrid-vesicles is confirmed by TEM and circular dichroism (CD) spectroscopy.

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Source
http://dx.doi.org/10.1002/mabi.202200522DOI Listing

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