Effects of the Hydrophilic N-Terminal Region on Aβ-Mediated Membrane Disruption.

ABSTRACT: Amyloidogenesis of amyloid-β (Aβ) peptides is intimately related to pathological neurodegeneration in Alzheimer's disease. Here, we investigated the membrane damage activity of Aβ40 and its derivatives that contain mutation at the N-terminal charged residues using a membrane leakage assay. A model 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) phospholipid vesicle encapsulating the fluorescent dye carboxyfluorescein was used in the study. Our results show that the mutations of the N-terminal charged residues of Aβ40 significantly affect the peptide-induced membrane leakage. The results suggest that favorable electrostatic interactions of the N-terminal charged residues and the phosphatidylcholine membrane surface are crucial in Aβ-mediated membrane permeation. The flexible and c

SUBMITTER: Morris C 

PROVIDER: S-EPMC9703304 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature