Gallic acid induced dose dependent inhibition of lysozyme fibrillation

Konar, Mouli; Bag, Sudipta; Roy, Pritam; Dasgupta, Swagata

doi:10.1016/j.ijbiomac.2017.05.158

Cited by 40 publications

(21 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Dynamic light scattering measurements were performed with the different peptide samples (oligomers and mature fibrils) on a Malvern nano zetasizer (Malvern, UK) using a laser source with λ = 633 nm and a detector at a scattering angle of θ = 173 degrees following previously reported method [14,43,72]. PHF6 and PHF6* peptides (25 µM) were incubated as described for the ThS assay, in the absence of the ThS dye, for 2 and 150 min to generate oligomers and mature fibrils, respectively, and the hydrodynamic diameter of them was immediately measured by DLS.…”

Section: Dynamic Light Scattering (Dls) Measurementsmentioning

confidence: 99%

Inhibition of tau amyloid formation and disruption of its preformed fibrils by Naphthoquinone–Dopamine hybrid

et al. 2021

View full text Add to dashboard Cite

Misfolding and aggregation of tau protein, into pathological amyloids, are hallmarks of a group of neurodegenerative diseases collectively termed tauopathies and their modulation may be therapeutically valuable. Herein, we describe the synthesis and characterization of a dopaminebased hybrid molecule, naphthoquinone-dopamine (NQDA). Using thioflavin S assay, CD, transmission electron microscopy, dynamic light scattering, Congo Red birefringence, and large unilamellar vesicle leakage assays, we demonstrated its efficacy in inhibiting the in vitro aggregation of key tau-derived amyloidogenic fragments, PHF6 (VQIVYK) and PHF6* (VQIINK), prime drivers of aggregation of full-length tau in disease pathology. Isothermal titration calorimetry analysis revealed that the interaction between NQDA and PHF6 is spontaneous and has significant binding efficiency driven by both entropic and enthalpic processes. Furthermore, NQDA efficiently disassembled preformed fibrils of PHF6 and PHF6* into nontoxic species. Molecular dynamic simulations supported the in vitro results and provided a plausible mode of binding of NQDA with PHF6 fibril. NQDA was also capable of inhibiting the aggregation of full-length tau protein and disrupting its preformed fibrils in vitro in a dose-dependent manner. In a comparative study, the IC 50 value (50% inhibition of fibril formation) of NQDA in inhibiting the aggregation of PHF6 (25 µM) was~17 µM, which is lower than for other bona fide amyloid inhibitors, naphthoquinone-tryptophan, rosmarinic acid, epigallocatechin gallate,~21,~77, or~19 µM, respectively. Comparable superiority of NQDA was observed for inhibition of PHF6*. These findings suggest that NQDA can be a useful scaffold for designing new therapeutics for Alzheimer's disease and other tauopathies.

show abstract

Section: Dynamic Light Scattering (Dls) Measurementsmentioning

confidence: 99%

Inhibition of tau amyloid formation and disruption of its preformed fibrils by Naphthoquinone–Dopamine hybrid

et al. 2021

View full text Add to dashboard Cite

show abstract

“…This could be the result of either fluorescence quenching due to molecule interactions or as an inner filter effect, because of the absorbance of ThT emissions by the inhibitor 25 . Despite this, multiple reports consider the reduction of ThT fluorescence as inhibition of aggregation [10][11][12]14,16,17,19,22,26 .…”

mentioning

confidence: 99%

“…The effect of GA is also usually determined in neutral pH both in vitro and in vivo 11,12,16,17,19,20,26 . And it is known that it is capable of undergoing oxidation at neutral and higher pH [26][27][28][29] . One report demonstrated that when this process is carried out at pH 7.4, a o-quinone is produced and changes in the solution's absorbance spectra can be observed 26 .…”

mentioning

confidence: 99%

Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils

Sakalauskas

Žiaunys

Smirnovas

2020

Sci Rep

View full text Add to dashboard Cite

Amyloidogenic protein assembly into insoluble fibrillar aggregates is linked with several neurodegenerative disorders, such as Alzheimer’s or Parkinson’s disease, affecting millions of people worldwide. The search for a potential anti-amyloid drug has led to the discovery of hundreds of compounds, none of which have passed all clinical trials. Gallic acid has been shown to both modulate factors leading to the onset of neurodegenerative disorders, as well as directly inhibit amyloid formation. However, the conditions under which this effect is seen could lead to oxidation of this polyphenol, likely changing its properties. Here we examine the effect of gallic acid and its oxidised form on the aggregation of a model amyloidogenic protein–insulin at low pH conditions. We show a vastly higher inhibitory potential of the oxidised form, as well as an alteration in the aggregation pathway, leading to the formation of a specific fibril conformation.

show abstract

“…The o-dihydroxy moiety of gallic acid is oxidized into quinone moiety. The quinone binds near the hydrophobic region of lysozyme and restricts hydrophobic exposure [19]. It has been shown that gallic acid passes into blood-brain barrier [12].…”

Section: Introductionmentioning

confidence: 99%

“…Rosmarinic acid prevents fibrillation of tau protein [3]. The percentages of inhi-bition of trypsin amyloid-like fibril formation changed proportionately with the concentrations of total phenolic compounds [19].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the formation of amyloid-like fibrils using herbal extracts

Kotormán

Kelemen

Kasi

et al. 2018

Acta Biologica Hungarica

View full text Add to dashboard Cite

We tested the amyloid fibril formation inhibitory effect of seven teas diluted in 55% ethanol at pH 7.0 at a protein concentration of 0.15 mg/ml α-chymotrypsin. In the experiments we investigated the formation and inhibition of amyloid fibrils by turbidity measurements, aggregation kinetics experiments and Congo red binding assay. The results suggest that the different teas effectively inhibit the formation of amyloidlike fibrils. The two most potent inhibitors were peppermint and melilot, extracts which almost completely inhibited the formation of aggregates in 5-fold dilution. The inhibitory effect on the aggregation formation of melilot and peppermint extracts was concentration dependant. The extent of inhibition was found to be proportional with the total concentration of phenolic compounds.

show abstract

Gallic acid induced dose dependent inhibition of lysozyme fibrillation

Cited by 40 publications

References 55 publications

Inhibition of tau amyloid formation and disruption of its preformed fibrils by Naphthoquinone–Dopamine hybrid

Inhibition of tau amyloid formation and disruption of its preformed fibrils by Naphthoquinone–Dopamine hybrid

Gallic acid oxidation products alter the formation pathway of insulin amyloid fibrils

Inhibition of the formation of amyloid-like fibrils using herbal extracts

Contact Info

Product

Resources

About