ArticleThe Journal of biological chemistry2011
Aromatic small molecules remodel toxic soluble oligomers of amyloid beta through three independent pathways.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 187 citations in OpenAlex.
- Epigallocatechin Gallate as a State-Dependent Modulator of Amyloid-Biomolecules · 2026Review
- Peptide-based therapeutics in the management of Alzheimer's disease (AD) and their potential to develop novel strategies.Metabolic brain disease · 2026Review
- K16F/E22F Mutation Promotes Oligomerization and Alters β-Sheet Topology of Aβ16-22 Peptides: Insights from Molecular Dynamics Simulations.ACS chemical neuroscience · 2026Article
- Searching potential GSK-3β inhibitors from marine sources using atomistic simulations.Molecular diversity · 2026Article
- Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics-Part B: Natural Compounds.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Plant-Based Inhibitors of Protein Aggregation.Biomolecules · 2025Review
- Inhibitory effect of Fisetin against the aggregation process of SOD1 E100K mutant: computer-based drug design as a potential therapeutic for ALS disease.Frontiers in chemistry · 2025Article
- Amphiphilic stilbene derivatives attenuate the neurotoxicity of soluble AβChemical science · 2022Article
- Based on molecular structures: Amyloid-β generation, clearance, toxicity and therapeutic strategies.Frontiers in molecular neuroscience · 2022Review
- Synergy of the Inhibitory Action of Polyphenols Plus Vitamin C on Amyloid Fibril Formation: Case Study of Human Stefin B.Antioxidants (Basel, Switzerland) · 2021Article
- Marine derivatives preventRoyal Society open science · 2021Article
- Modulation of Neuroinflammation by the Gut Microbiota in Prion and Prion-Like Diseases.Pathogens (Basel, Switzerland) · 2021Review
- Review
- Natural Products Targeting Amyloid Beta in Alzheimer's Disease.International journal of molecular sciences · 2021Review
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
- Flavonoids as an Intervention for Alzheimer's Disease: Progress and Hurdles Towards Defining a Mechanism of Action.Brain plasticity (Amsterdam, Netherlands) · 2021Review
- Squalamine and Its Derivatives Modulate the Aggregation of Amyloid-β and α-Synuclein and Suppress the Toxicity of Their Oligomers.Frontiers in neuroscience · 2021Article
- Mechanism of human γD-crystallin protein aggregation in UV-C light.Molecular vision · 2021Article
- Therapeutic Strategies to Reduce the Toxicity of Misfolded Protein Oligomers.International journal of molecular sciences · 2020Review
- Small molecule induced toxic human-IAPP species characterized by NMR.Chemical communications (Cambridge, England) · 2020Article
10 more citing papers are in PubMed but not listed here.
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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
In protein conformational disorders ranging from Alzheimer to Parkinson disease, proteins of unrelated sequence misfold into a similar array of aggregated conformers ranging from small oligomers to large amyloid fibrils. Substantial evidence suggests that small, prefibrillar oligomers are the most toxic species, yet to what extent they can be selectively targeted and remodeled into non-toxic conformers using small molecules is poorly understood. We have evaluated the conformational specificity and remodeling pathways of a diverse panel of aromatic small molecules against mature soluble oligomers of the Aβ42 peptide associated with Alzheimer disease. We find that small molecule antagonists can be grouped into three classes, which we herein define as Class I, II, and III molecules, based on the distinct pathways they utilize to remodel soluble oligomers into multiple conformers with reduced toxicity. Class I molecules remodel soluble oligomers into large, off-pathway aggregates that are non-toxic. Moreover, Class IA molecules also remodel amyloid fibrils into the same off-pathway structures, whereas Class IB molecules fail to remodel fibrils but accelerate aggregation of freshly disaggregated Aβ. In contrast, a Class II molecule converts soluble Aβ oligomers into fibrils, but is inactive against disaggregated and fibrillar Aβ. Class III molecules disassemble soluble oligomers (as well as fibrils) into low molecular weight species that are non-toxic. Strikingly, Aβ non-toxic oligomers (which are morphologically indistinguishable from toxic soluble oligomers) are significantly more resistant to being remodeled than Aβ soluble oligomers or amyloid fibrils. Our findings reveal that relatively subtle differences in small molecule structure encipher surprisingly large differences in the pathways they employ to remodel Aβ soluble oligomers and related aggregated conformers.
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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.