ArticleACS chemical neuroscience2012
A key role for lysine residues in amyloid β-protein folding, assembly, and toxicity.
Article in ACS chemical neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 121 citations in OpenAlex.
- Trial
- Effect of the Tottori familial disease mutation (D7N) on the monomers and dimers of Aβ40 and Aβ42.ACS chemical neuroscience · 2013Trial
- Lysine-Targeting Inhibitors of Amyloidogenic Protein Aggregation: A Promise for Neurodegenerative Proteinopathies.JACS Au · 2025Review
- Formation of a β-Endorphin Corona Mitigates Alzheimer's Amyloidogenesis.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Leveraging heterocycle-fused 1,4-benzoquinone to design chemical modulators for both metal-free and metal-bound amyloid-β.Chemical science · 2025Article
- ALZ-801 prevents amyloid β-protein assembly and reduces cytotoxicity: A preclinical experimental study.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Synthesis, biological evaluation and metadynamics simulations of novelRSC medicinal chemistry · 2024Article
- Understanding the mechanisms of green tea EGCG against amyloid β oligomer neurotoxicity through computational studies.RSC advances · 2024Article
- Human cystatin C induces the disaggregation process of selected amyloid beta peptides: a structural and kinetic view.Scientific reports · 2023Article
- Investigating the Effects of the POPC-POPG Lipid Bilayer Composition on PAP248-286 Binding Using CG Molecular Dynamics Simulations.The journal of physical chemistry. B · 2023Article
- Designing multi-target-directed flavonoids: a strategic approach to Alzheimer's disease.Chemical science · 2023Article
- Molecular Tweezers: Supramolecular Hosts with Broad-Spectrum Biological Applications.Pharmacological reviews · 2023Review
- A coarse-grained molecular dynamics investigation on spontaneous binding of AβComputational and structural biotechnology journal · 2023Article
- E. coli biosensor based on modular GFP and luxI/luxR cyclic amplification circuit for sensitive detection of lysine.Analytical and bioanalytical chemistry · 2022Article
- Amyloidogenesis: What Do We Know So Far?International journal of molecular sciences · 2022Review
- Specific Mutations in the Cholesterol-Binding Site of APP Alter Its Processing and Favor the Production of Shorter, Less Toxic Aβ Peptides.Molecular neurobiology · 2022Article
- Epitope alteration by small molecules and applications in drug discovery.Chemical science · 2022Article
- Evolution and co-evolution: insights into the divergence of plant heat shock factor genes.Physiology and molecular biology of plants : an international journal of functional plant biology · 2022Article
- Altered succinylation of mitochondrial proteins, APP and tau in Alzheimer's disease.Nature communications · 2022Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A combination of hydrophobic and electrostatic interactions is important in initiating the aberrant self-assembly process that leads to formation of toxic oligomers and aggregates by multiple disease-related proteins, including amyloid β-protein (Aβ), whose self-assembly is believed to initiate brain pathogenesis in Alzheimer's disease. Lys residues play key roles in this process and participate in both types of interaction. They also are the target of our recently reported molecular tweezer inhibitors. To obtain further insight into the role of the two Lys residues in Aβ assembly and toxicity, here we substituted each by Ala in both Aβ40 and Aβ42 and studied the impact of the substitution on Aβ oligomerization, aggregation, and toxicity. Our data show that each substitution has a major impact on Aβ assembly and toxicity, with significant differences depending on peptide length (40 versus 42 amino acids) and the position of the substitution. In particular, Lys16→Ala substitution dramatically reduces Aβ toxicity. The data support the use of compounds targeting Lys residues specifically as inhibitors of Aβ toxicity and suggest that exploring the role of Lys residues in other disease-related amyloidogenic proteins may help understanding the mechanisms of aggregation and toxicity of these proteins.
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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.