1. Inhibition of amyloid beta-induced synaptotoxicity by a pentapeptide derived from the glycine zipper region of the neurotoxic peptide
- Author
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Carlos F. Burgos, Juan C. Urrutia, Carolina Castillo, Luis G. Aguayo, Eduardo J Fernández-Pérez, Christian Peters, María Paz Espinoza, Carlos Opazo, and Victor A. Streltsov
- Subjects
Aging ,Amyloid beta ,Membrane lipids ,Glycine ,Synaptic Transmission ,Pentapeptide repeat ,Synaptic vesicle ,Cell membrane ,Membrane Lipids ,Alzheimer Disease ,medicine ,Humans ,Molecular Targeted Therapy ,Lipid bilayer ,Cells, Cultured ,Amyloid beta-Peptides ,biology ,Chemistry ,General Neuroscience ,Vesicle ,Cell Membrane ,P3 peptide ,Brain ,Neuroprotective Agents ,medicine.anatomical_structure ,Biochemistry ,Biophysics ,biology.protein ,Calcium ,Synaptic Vesicles ,Neurology (clinical) ,Geriatrics and Gerontology ,Oligopeptides ,Developmental Biology - Abstract
A major characteristic of Alzheimer's disease is the presence of amyloid beta (Aβ) oligomers and aggregates in the brain. Aβ oligomers interact with the neuronal membrane inducing perforations, causing an influx of calcium ions and increasing the release of synaptic vesicles that leads to a delayed synaptic failure by vesicle depletion. Here, we identified a neuroprotective pentapeptide anti-Aβ compound having the sequence of the glycine zipper region of the C-terminal of Aβ (G33LMVG37). Docking and Förster resonance energy transfer experiments showed that G33LMVG37 interacts with Aβ at the C-terminal region, which is important for Aβ association and insertion into the lipid membrane. Furthermore, this pentapeptide interfered with Aβ aggregation, association, and perforation of the plasma membrane. The synaptotoxicity induced by Aβ after acute and chronic applications were abolished by G33LMVG37. These results provide a novel rationale for drug development against Alzheimer's disease.
- Published
- 2013
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