ArticleBiochemistry and biophysics reports2015
Transthyretin chemical chaperoning by flavonoids: Structure-activity insights towards the design of potent amyloidosis inhibitors.
Article in Biochemistry and biophysics reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Article
- Members of the GADD45 Protein Family Show Distinct Propensities to form Toxic Amyloid-Like Aggregates in Physiological Conditions.International journal of molecular sciences · 2021Article
- Chemical Chaperones Modulate the Formation of Metabolite Assemblies.International journal of molecular sciences · 2021Article
- Activity of Selected Group of Monoterpenes in Alzheimer's Disease Symptoms in Experimental Model Studies-A Non-Systematic Review.International journal of molecular sciences · 2021Review
- Nutritional Value ofNutrients · 2021Article
- Transthyretin Misfolding, A Fatal Structural Pathogenesis Mechanism.International journal of molecular sciences · 2021Review
- Gene Regulation of Biofilm-Associated Functional Amyloids.Pathogens (Basel, Switzerland) · 2021Review
- Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis.International journal of molecular sciences · 2021Article
- Article
- Aggregation of Mouse Serum Amyloid A Protein Was Promoted by Amyloid-Enhancing Factors with the More Genetically Homologous Serum Amyloid A.International journal of molecular sciences · 2021Article
- A serine protease secreted from Bacillus subtilis cleaves human plasma transthyretin to generate an amyloidogenic fragment.Communications biology · 2020Article
- Oligomerization Profile of Human Transthyretin Variants with Distinct Amyloidogenicity.Molecules (Basel, Switzerland) · 2020Article
- Structural Stabilization of Human Transthyretin byBiomolecules · 2019Article
- Uncovering the Neuroprotective Mechanisms of Curcumin on Transthyretin Amyloidosis.International journal of molecular sciences · 2019Review
- The interaction of several herbal extracts with α-synuclein: Fibril formation and surface plasmon resonance analysis.PloS one · 2019Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMany polyphenols have been proposed as broad-spectrum inhibitors of amyloid formation. To investigate structure-activity relationships relevant for the interaction of flavonoids with transthyretin (TTR), the protein associated with familial amyloid polyneuropathy (FAP), we compared the effects of major tea catechins and their larger polymers theaflavins, side-by-side, on TTR amyloid formation process.
methodsInteraction of flavonoids with TTR and effect on TTR stability were assessed through binding assays and isoelectric focusing in polyacrylamide gel. TTR aggregation was studied, in vitro, by dynamic light scattering (DLS), transmission electron microscopy (TEM) and in cell culture, through cytotoxicity assays.
resultsTested flavonoids bound to TTR and stabilized the TTR tetramer, with different potencies. The flavonoids also inhibited in vitro formation of TTR small oligomeric species and in cell culture inhibited pathways involving caspase-3 activation and ER stress that are induced by TTR oligomers. In all assays performed the galloyl esters presented higher potency to inhibit aggregation than the non-gallated flavonoids tested.
conclusionsOur results highlight the presence of gallate ester moiety as key structural feature of flavonoids in chemical chaperoning of TTR aggregation. Upon binding to the native tetramer, gallated flavonoids redirect the TTR amyloidogenic pathway into unstructured nontoxic aggregation assemblies more efficiently than their non-gallated forms. GENERAL SIGNIFICANCE: Our findings suggest that galloyl moieties greatly enhance flavonoid anti-amyloid chaperone activity and this should be taken into consideration in therapeutic candidate drug discovery.
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