ArticlePloS one2013
Stability of transmembrane amyloid β-peptide and membrane integrity tested by molecular modeling of site-specific Aβ42 mutations.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- Inward opening (IO) to outward opening (OO) 'catalytic transition' and OO to IO 'relaxation' of P-glycoprotein: to investigate the role of helices in efflux through targeted molecular dynamics simulation.In silico pharmacology · 2025Article
- 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
- An Overview of Several Inhibitors for Alzheimer's Disease: Characterization and Failure.International journal of molecular sciences · 2021Review
- Effects of the Hydrophilic N-Terminal Region on Aβ-Mediated Membrane Disruption.The journal of physical chemistry. B · 2021Article
- Coarse-grained MD simulations reveal beta-amyloid fibrils of various sizes bind to interfacial liquid-ordered and liquid-disordered regions in phase separated lipid rafts with diverse membrane-bound conformational states.Biophysical chemistry · 2020Article
- Computer simulations of protein-membrane systems.Progress in molecular biology and translational science · 2020Article
- N-Terminal Charged Residues of Amyloid-β Peptide Modulate Amyloidogenesis and Interaction with Lipid Membrane.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- Insights into the Molecular Mechanisms of Alzheimer's and Parkinson's Diseases with Molecular Simulations: Understanding the Roles of Artificial and Pathological Missense Mutations in Intrinsically Disordered Proteins Related to Pathology.International journal of molecular sciences · 2018Review
- Article
- Maximally asymmetric transbilayer distribution of anionic lipids alters the structure and interaction with lipids of an amyloidogenic protein dimer bound to the membrane surface.Chemistry and physics of lipids · 2016Article
- Amyloid β Protein and Alzheimer's Disease: When Computer Simulations Complement Experimental Studies.Chemical reviews · 2015Review
- Modulation of Alzheimer's Aβ protofilament-membrane interactions by lipid headgroups.ACS chemical neuroscience · 2015Article
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- The interaction between amyloid-β peptides and anionic lipid membranes containing cholesterol and melatonin.PloS one · 2014Article
- Membrane permeation induced by aggregates of human islet amyloid polypeptides.Biophysical journal · 2013Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interactions of the amyloid β-protein (Aβ) with neuronal cell membranes, leading to the disruption of membrane integrity, are considered to play a key role in the development of Alzheimer's disease. Natural mutations in Aβ42, such as the Arctic mutation (E22G) have been shown to increase Aβ42 aggregation and neurotoxicity, leading to the early-onset of Alzheimer's disease. A correlation between the propensity of Aβ42 to form protofibrils and its effect on neuronal dysfunction and degeneration has been established. Using rational mutagenesis of the Aβ42 peptide it was further revealed that the aggregation of different Aβ42 mutants in lipid membranes results in a variety of polymorphic aggregates in a mutation dependent manner. The mutant peptides also have a variable ability to disrupt bilayer integrity. To further test the connection between Aβ42 mutation and peptide-membrane interactions, we perform molecular dynamics simulations of membrane-inserted Aβ42 variants (wild-type and E22G, D23G, E22G/D23G, K16M/K28M and K16M/E22G/D23G/K28M mutants) as β-sheet monomers and tetramers. The effects of charged residues on transmembrane Aβ42 stability and membrane integrity are analyzed at atomistic level. We observe an increased stability for the E22G Aβ42 peptide and a decreased stability for D23G compared to wild-type Aβ42, while D23G has the largest membrane-disruptive effect. These results support the experimental observation that the altered toxicity arising from mutations in Aβ is not only a result of the altered aggregation propensity, but also originates from modified Aβ interactions with neuronal membranes.
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