ArticleProceedings of the National Academy of Sciences of the United States of America2019
α-Sheet secondary structure in amyloid β-peptide drives aggregation and toxicity in Alzheimer's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 147 citations in OpenAlex.
- De Novo Autogenic Engineered Living Functional Materials.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Targeting soluble misfolded oligomers in anti-amyloid research.Nature reviews. Chemistry · 2026Review
- Analysis of amyloid beta oligomers by cyclic ion mobility-mass spectrometry.Analytical and bioanalytical chemistry · 2026Article
- The amino acid substitutions A30W, K28A, and M35C alter amyloid-β peptide toxicity in cell culture and in anFrontiers in aging neuroscience · 2026Article
- Copper homeostasis and cuproptosis in Alzheimer's disease (Review).International journal of molecular medicine · 2025Review
- Rationally Designed Pentapeptide Analogs of Aβ19-23 Fragment as Potent Inhibitors of Aβ42 Aggregation.Molecules (Basel, Switzerland) · 2025Article
- Nitroxyl Hybrids with Curcumin and Stilbene Scaffolds Display Potent Antioxidant Activity, Remodel the Amyloid Beta Oligomer, and Reverse Amyloid Beta-Induced Cytotoxicity.Antioxidants (Basel, Switzerland) · 2024Article
- Key charged residues influence the amyloidogenic propensity of the helix-1 region of serum amyloid A.Biochimica et biophysica acta. General subjects · 2024Article
- Hybrid Amyloid Quantum Dot Nano-Bio Assemblies to Probe Neuroinflammatory Damage.ACS chemical neuroscience · 2024Article
- Designed De Novo α-Sheet Peptides Destabilize Bacterial Biofilms and Increase the Susceptibility ofInternational journal of molecular sciences · 2024Article
- Neuroinflammation in Alzheimer's disease: insights from peripheral immune cells.Immunity & ageing : I & A · 2024Review
- Performance of SOBA-AD blood test in discriminating Alzheimer's disease patients from cognitively unimpaired controls in two independent cohorts.Scientific reports · 2024Article
- An overview on glycation: molecular mechanisms, impact on proteins, pathogenesis, and inhibition.Biophysical reviews · 2024Review
- Alzheimer's Disease: A Molecular Model and Implied Path to Improved Therapy.International journal of molecular sciences · 2024Review
- Mechanistic insights into the role of amyloid-β in innate immunity.Scientific reports · 2024Article
- Delineating the Role of GxxxG Motif in Amyloidogenesis: A New Perspective in Targeting Amyloid-Beta Mediated AD Pathogenesis.ACS bio & med chem Au · 2024Review
- Human islet amyloid polypeptide-induced β-cell cytotoxicity is linked to formation of α-sheet structure.Protein science : a publication of the Protein Society · 2024Article
- Noninvasive Treatment of Alzheimer's Disease with Scintillating Nanotubes.Advanced healthcare materials · 2023Article
- In Situ Raman Study of Neurodegenerated Human Neuroblastoma Cells Exposed to Outer-Membrane Vesicles Isolated fromInternational journal of molecular sciences · 2023Article
- Effect of Vitamin E on Transcriptomic Alterations in Alzheimer's Disease.International journal of molecular sciences · 2023Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Alzheimer's disease (AD) is characterized by the deposition of β-sheet-rich, insoluble amyloid β-peptide (Aβ) plaques; however, plaque burden is not correlated with cognitive impairment in AD patients; instead, it is correlated with the presence of toxic soluble oligomers. Here, we show, by a variety of different techniques, that these Aβ oligomers adopt a nonstandard secondary structure, termed "α-sheet." These oligomers form in the lag phase of aggregation, when Aβ-associated cytotoxicity peaks, en route to forming nontoxic β-sheet fibrils. De novo-designed α-sheet peptides specifically and tightly bind the toxic oligomers over monomeric and fibrillar forms of Aβ, leading to inhibition of aggregation in vitro and neurotoxicity in neuroblastoma cells. Based on this specific binding, a soluble oligomer-binding assay (SOBA) was developed as an indirect probe of α-sheet content. Combined SOBA and toxicity experiments demonstrate a strong correlation between α-sheet content and toxicity. The designed α-sheet peptides are also active in vivo where they inhibit Aβ-induced paralysis in a transgenic Aβ
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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.