ArticleScientific reports2015
Brazilin inhibits amyloid β-protein fibrillogenesis, remodels amyloid fibrils and reduces amyloid cytotoxicity.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 162 citations in OpenAlex.
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- Hesperetin reduces neuronal death in an SHSY5Y Alzheimer's model by inhibiting inflammation and apoptosis and pyroptosis cell death pathways.Scientific reports · 2025Article
- Nanoplasmonic Infrared Microarray Sensor Enabling Structural Protein Biomarker-Based Drug Screening for Neurodegenerative Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 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
- Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics-Part A: Endogenous Compounds and Repurposed Drugs.Pharmaceuticals (Basel, Switzerland) · 2025Review
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- Tetracyclic homoisoflavanoid (+)-brazilin: a natural product inhibits c-di-AMP-producing enzyme andMicrobiology spectrum · 2024Article
- Adenosine triphosphate induces amorphous aggregation of amyloid β by increasing Aβ dynamics.Scientific reports · 2024Article
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
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- Unveiling the therapeutic potential ofFrontiers in pharmacology · 2024Article
- Natural Compounds as Inhibitors of Aβ Peptide and Tau Aggregation.CNS & neurological disorders drug targets · 2024Review
- Effect of Bacterial Amyloid Protein Phenol-Soluble Modulin Alpha 3 on the Aggregation of Amyloid Beta Protein Associated with Alzheimer's Disease.Biomimetics (Basel, Switzerland) · 2023Article
- Phytochemical Interactions with Calmodulin and Critical Calmodulin Binding Proteins Involved in Amyloidogenesis in Alzheimer's Disease.Biomolecules · 2023Review
- New Insights into Alzheimer's Disease: Novel Pathogenesis, Drug Target and Delivery.Pharmaceutics · 2023Review
- Partial Destabilization of Amyloid-β Protofibril by Methionine Photo-Oxidation: A Molecular Dynamic Simulation Study.ACS omega · 2023Article
- Therapeutic roles of plants for 15 hypothesised causal bases of Alzheimer's disease.Natural products and bioprospecting · 2022Article
- Stable Cavitation Interferes with AβJournal of chemical information and modeling · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Soluble amyloid β-protein (Aβ) oligomers, the main neurotoxic species, are predominantly formed from monomers through a fibril-catalyzed secondary nucleation. Herein, we virtually screened an in-house library of natural compounds and discovered brazilin as a dual functional compound in both Aβ42 fibrillogenesis inhibition and mature fibril remodeling, leading to significant reduction in Aβ42 cytotoxicity. The potent inhibitory effect of brazilin was proven by an IC50 of 1.5 ± 0.3 μM, which was smaller than that of (-)-epigallocatechin gallate in Phase III clinical trials and about one order of magnitude smaller than those of curcumin and resveratrol. Most importantly, it was found that brazilin redirected Aβ42 monomers and its mature fibrils into unstructured Aβ aggregates with some β-sheet structures, which could prevent both the primary nucleation and the fibril-catalyzed secondary nucleation. Molecular simulations demonstrated that brazilin inhibited Aβ42 fibrillogenesis by directly binding to Aβ42 species via hydrophobic interactions and hydrogen bonding and remodeled mature fibrils by disrupting the intermolecular salt bridge Asp23-Lys28 via hydrogen bonding. Both experimental and computational studies revealed a different working mechanism of brazilin from that of known inhibitors. These findings indicate that brazilin is of great potential as a neuroprotective and therapeutic agent for Alzheimer's disease.
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