ArticleBiochemistry2012
Probing structural features of Alzheimer's amyloid-β pores in bilayers using site-specific amino acid substitutions.
Article in Biochemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 56 citations in OpenAlex.
- Pathological calcium influx through amyloid beta pores disrupts synaptic function.Cell calcium · 2025Article
- Amyloid β 1-42 Can Form Ion Channels as Small as Gramicidin in Model Lipid Membranes.Membranes · 2025Article
- Modulation of Lipid Dynamics in the β-Amyloid Aggregates Induced Membrane Fragmentation.The journal of physical chemistry. B · 2024Article
- Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease.Angewandte Chemie (Weinheim an der Bergstrasse, Germany) · 2023Review
- Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease.Angewandte Chemie (International ed. in English) · 2023Review
- In-cellBiophysical chemistry · 2023Article
- Molecular insights into the primary nucleation of polymorphic amyloid β dimers in DOPC lipid bilayer membrane.Protein science : a publication of the Protein Society · 2022Article
- NMR Studies of the Ion Channel-Forming Human Amyloid-β with Zinc Ion Concentrations.Membranes · 2021Article
- Time-Dependent Lipid Dynamics, Organization and Peptide-Lipid Interaction in Phospholipid Bilayers with Incorporated β-Amyloid Oligomers.The journal of physical chemistry letters · 2020Article
- Humanin Blocks the Aggregation of Amyloid-β Induced by Acetylcholinesterase, an Effect Abolished in the Presence of IGFBP-3.Biochemistry · 2020Article
- Progress in supercapacitors: roles of two dimensional nanotubular materials.Nanoscale advances · 2020Review
- The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.EMBO molecular medicine · 2018Article
- Amyloid β Ion Channels in a Membrane Comprising Brain Total Lipid Extracts.ACS chemical neuroscience · 2017Article
- Ion Channel Formation by Amyloid-β42 Oligomers but Not Amyloid-β40 in Cellular Membranes.The Journal of biological chemistry · 2017Article
- Small molecule NPT-440-1 inhibits ionic flux through AβNanomedicine : nanotechnology, biology, and medicine · 2016Article
- Interaction of toxic and non-toxic HypF-N oligomers with lipid bilayers investigated at high resolution with atomic force microscopy.Oncotarget · 2016Article
- The higher level of complexity of K-Ras4B activation at the membrane.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Computational Methods for Structural and Functional Studies of Alzheimer's Amyloid Ion Channels.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Mechanisms of membrane binding of small GTPase K-Ras4B farnesylated hypervariable region.The Journal of biological chemistry · 2015Article
- Ligand-receptor interaction catalyzes the aggregation of small molecules to induce cell necroptosis.Journal of the American Chemical Society · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
A current hypothesis for the pathology of Alzheimer's disease (AD) proposes that amyloid-β (Aβ) peptides induce uncontrolled, neurotoxic ion flux across cellular membranes. The mechanism of ion flux is not fully understood because no experiment-based Aβ channel structures at atomic resolution are currently available (only a few polymorphic states have been predicted by computational models). Structural models and experimental evidence lend support to the view that the Aβ channel is an assembly of loosely associated mobile β-sheet subunits. Here, using planar lipid bilayers and molecular dynamics (MD) simulations, we show that amino acid substitutions can be used to infer which residues are essential for channel structure. We created two Aβ(1-42) peptides with point mutations: F19P and F20C. The substitution of Phe19 with Pro inhibited channel conductance. MD simulation suggests a collapsed pore of F19P channels at the lower bilayer leaflet. The kinks at the Pro residues in the pore-lining β-strands induce blockage of the solvated pore by the N-termini of the chains. The cysteine mutant is capable of forming channels, and the conductance behavior of F20C channels is similar to that of the wild type. Overall, the mutational analysis of the channel activity performed in this work tests the proposition that the channels consist of a β-sheet rich organization, with the charged/polar central strand containing the mutation sites lining the pore, and the C-terminal strands facing the hydrophobic lipid tails. A detailed understanding of channel formation and its structure should aid studies of drug design aiming to control unregulated Aβ-dependent ion fluxes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.