We investigate the role played by membrane composition on the interaction and self-assembly of b-amyloid peptide (AbP1–40) during pore formation in planar lipid membranes (PLMs). Incorporation studies showed that AbP does not interact with zwitterionic membranes made up of phosphatidylcholine, whereas the addition of cholesterol or ergosterol to the membranes leads to channel formation. Among the PLMs used, a higher propensity of AbP to form channels at low applied potential (620 mV) was observed in 7-dehydrocholesterol and in oxidized cholesterol PLMs. These channels present long lifetimes, high-occurrence frequencies, and are voltage dependent. In particular, the AbP channel in oxidized cholesterol showed anion selectivity. Thus cholesterol (and sterols in general) could be considered as targets for AbP, which prevents the fibrillation process by increasing incorporation into membranes. Furthermore, by switching the channel selectivity versus anions, cholesterol helps to reduce the imbalance of the cellular ions, calcium included, induced by membrane depolarization, which could be one of the factors responsible for cytotoxicity in Alzheimer’s disease.

Effect of sterols on beta-amyloid peptide (AbetaP 1-40) channel formation and their properties in planar lipid membranes

S. MICELLI;MELELEO D.;V. PICCIARELLI;E. GALLUCCI
2004

Abstract

We investigate the role played by membrane composition on the interaction and self-assembly of b-amyloid peptide (AbP1–40) during pore formation in planar lipid membranes (PLMs). Incorporation studies showed that AbP does not interact with zwitterionic membranes made up of phosphatidylcholine, whereas the addition of cholesterol or ergosterol to the membranes leads to channel formation. Among the PLMs used, a higher propensity of AbP to form channels at low applied potential (620 mV) was observed in 7-dehydrocholesterol and in oxidized cholesterol PLMs. These channels present long lifetimes, high-occurrence frequencies, and are voltage dependent. In particular, the AbP channel in oxidized cholesterol showed anion selectivity. Thus cholesterol (and sterols in general) could be considered as targets for AbP, which prevents the fibrillation process by increasing incorporation into membranes. Furthermore, by switching the channel selectivity versus anions, cholesterol helps to reduce the imbalance of the cellular ions, calcium included, induced by membrane depolarization, which could be one of the factors responsible for cytotoxicity in Alzheimer’s disease.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11586/79628
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