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Effect of Sterols on ß-Amyloid Peptide (AßP 1–40) Channel Formation and their Properties in Planar Lipid Membranes

Silvia Micelli ^*, Daniela Meleleo ^*, Vittorio Picciarelli  and Enrico Gallucci ^*

^* Dipartimento Farmaco-Biologico and Dipartimento Interateneo di Fisica, Università degli Studi di Bari, 70126 Bari, Italy

Correspondence: Address reprint requests to Silvia Micelli, E-mail: micelli{at}farmbiol.uniba.it

We investigate the role played by membrane composition on the interaction and self-assembly of ß-amyloid peptide (AßP1–40) during pore formation in planar lipid membranes (PLMs). Incorporation studies showed that AßP 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 AßP to form channels at low applied potential (±20 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 AßP channel in oxidized cholesterol showed anion selectivity. Thus cholesterol (and sterols in general) could be considered as targets for AßP, 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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