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Nature Of The Neurotoxic Membrane Actions Of Amyloid-Β On Hippocampal Neurons In Alzheimer's Disease, Fernando J. Sepúlveda, Humberto Fierro, Eduardo Fernandez, Carolina Castillo, Robert W. Peoples, Carlos Opazo, Luis G. Aguayo

Biomedical Sciences Faculty Research and Publications

The mechanism by which amyloid-β (Aβ) produces brain dysfunction in patients with Alzheimer's disease is largely unknown. According to previous studies, Aβ might share perforating properties with gramicidin, a well-accepted membrane-disrupting peptide. Therefore, we hypothesize that the key steps leading to synaptotoxicity by Aβ and gramicidin involve peptide aggregation, pore formation, and calcium dysregulation. Here, we show that Aβ and gramicidin form aggregates enriched in β-sheet structures using electron microscopy, and Thioflavin and Congo Red staining techniques. Also, we found that Aβ and gramicidin display fairly similar actions in hippocampal cell membranes, i.e. inducing Ca²⁺ entry and synaptoxicity characterized …