title: Inhibition of amyloid beta-induced synaptotoxicity by a pentapeptide derived from the glycine zipper region of the neurotoxic peptide.
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.
authors.affiliation: Laboratory of Neurophysiology, Department of Physiology, University of Concepción, Concepción, Chile; Laboratory of Neurobiometals, Department of Physiology, University of Concepción, Concepción, Chile.
authors.forename: Christian
authors.initials: C
authors.lastname: Peters
authors.forename: Eduardo J
authors.initials: EJ
authors.lastname: Fernandez-Perez
authors.forename: Carlos F
authors.initials: CF
authors.lastname: Burgos
authors.forename: María P
authors.initials: MP
authors.lastname: Espinoza
authors.forename: Carolina
authors.initials: C
authors.lastname: Castillo
authors.forename: Juan C
authors.initials: JC
authors.lastname: Urrutia
authors.forename: Victor A
authors.initials: VA
authors.lastname: Streltsov
authors.forename: Carlos
authors.initials: C
authors.lastname: Opazo
authors.forename: Luis G
authors.initials: LG
authors.lastname: Aguayo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005998:Glycine / Q000737:chemistry*; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D058990:Molecular Targeted Therapy; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology*; D009842:Oligopeptides / Q000737:chemistry* / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D008563:Membrane Lipids; D018696:Neuroprotective Agents; D009842:Oligopeptides; D002118:Calcium; D005998:Glycine
keywords: Alzheimer; Beta Amyloid; Oligomers; Pore; Synaptic Toxicity