Two polyphenols with diverse mechanisms towards amyloidosis: differential modulation of the fibrillation pathway of human lysozyme by curcumin and EGCG

Zaidi, Fatima; Bhat, Rajiv

doi:10.1080/07391102.2020.1860824

Cited by 8 publications

(4 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The interaction between HEWL and solution was not shielded by VAL when present at a concentration 10-fold lower than HEWL, however, this could be possible when VAL was present at a 1:1 M ratio. In all reaction mixtures containing 1% DMSO, hydrophobic VAL was prepared in DMSO, and this amount of DMSO had no significant effect on protein accumulation [ 76 , 77 ].…”

Section: Resultsmentioning

confidence: 99%

The effect of novel antihypertensive drug valsartan on lysozyme aggregation: A combined in situ and in silico study

Altwaijry¹,

Almutairi²,

Khan³

et al. 2023

Heliyon

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

The effect of novel antihypertensive drug valsartan on lysozyme aggregation: A combined in situ and in silico study

Altwaijry¹,

Almutairi²,

Khan³

et al. 2023

Heliyon

View full text Add to dashboard Cite

“…A few previous studies also validate ANS’s binding to soluble aggregate [ 56 , 57 ]. The hydrophobic CTZ was prepared in DMSO and all reaction mixtures contained 1% of DMSO and this was not observed to have a significant effect on protein accumulation [ 58 , 59 ]. To gain further insight into structural details and the mode of interaction between HEWL and CTZ at the atomic level, molecular docking and simulation were conducted.…”

Section: Discussionmentioning

confidence: 99%

Effect of Antihypertensive Drug (Chlorothiazide) on Fibrillation of Lysozyme: A Combined Spectroscopy, Microscopy, and Computational Study

Altwaijry

Almutairi

Khan

et al. 2023

IJMS

View full text Add to dashboard Cite

Amyloid fibrils abnormally accumulate together in the human body under certain conditions, which can result in lethal conditions. Thus, blocking this aggregation may prevent or treat this disease. Chlorothiazide (CTZ) is a diuretic and is used to treat hypertension. Several previous studies suggest that diuretics prevent amyloid-related diseases and reduce amyloid aggregation. Thus, in this study we examine the effects of CTZ on hen egg white lysozyme (HEWL) aggregation using spectroscopic, docking, and microscopic approaches. Our results showed that under protein misfolding conditions of 55 °C, pH 2.0, and 600 rpm agitation, HEWL aggregated as evidenced by the increased turbidity and Rayleigh light scattering (RLS). Furthermore, thioflavin-T, as well as trans electron microscope (TEM) analysis confirmed the formation of amyloid structures. An anti-aggregation effect of CTZ is observed on HEWL aggregations. Circular dichroism (CD), TEM, and Thioflavin-T fluorescence show that both CTZ concentrations reduce the formation of amyloid fibrils as compared to fibrillated. The turbidity, RLS, and ANS fluorescence increase with CTZ increasing. This increase is attributed to the formation of a soluble aggregation. As evidenced by CD analysis, there was no significant difference in α-helix content and β-sheet content between at 10 µM CTZ and 100 µM. A TEM analysis of HEWL coincubated with CTZ at different concentrations validated all the above-mentioned results. The TEM results show that CTZ induces morphological changes in the typical structure of amyloid fibrils. The steady-state quenching study demonstrated that CTZ and HEWL bind spontaneously via hydrophobic interactions. HEWL–CTZ also interacts dynamically with changes in the environment surrounding tryptophan. Computational results revealed the binding of CTZ to ILE98, GLN57, ASP52, TRP108, TRP63, TRP63, ILE58, and ALA107 residues in HEWL via hydrophobic interactions and hydrogen bonds with a binding energy of −6.58 kcal mol−1. We suggest that at 10 µM and 100 μM, CTZ binds to the aggregation-prone region (APR) of HEWL and stabilizes it, thus preventing aggregation. Based on these findings, we can conclude that CTZ has antiamyloidogenic activity and can prevent fibril aggregation.

show abstract

“…As stated above, several studies examined the possibilities of small molecules, including different classes of drugs, polyphenols, ,,, and glycolacridines, as plausible inhibitors of amyloid fibrillation. However, no study is conducted on furosemide (FUR), a benzoic sulfonamide furan, which inhibits water reabsorption by competitively binding to sodium–potassium–chloride cotransporter.…”

Section: Introductionmentioning

confidence: 99%

“…Rottlerin dissolves preformed amyloid in HEWL . Curcumin also reported to interfere with ß-amyloid, synuclein, , and HL fibrils by binding to small amyloid species to block aggregation and fibril formation in vitro . Resveratrol interferes with an early step in the fibrillization pathway of HL by binding with weak to moderate affinity to the conformations populated at the early stages of the pathway with concomitant stabilization of these initial conformations .…”

Section: Introductionmentioning

confidence: 99%

Furosemide Derails Human Lysozyme Fibrillation by Interacting with Aggregation Hot Spots: A Biophysical Comprehension

Zaidi,

Ahmad,

Khursheed

et al. 2024

J. Phys. Chem. B

View full text Add to dashboard Cite

Kidney-associated human lysozyme amyloidosis leads to renal impairments;thus, patients are often prescribed furosemide. Based on this fact, the effect of furosemide on induced human lysozyme fibrillation, in vitro, is evaluated by spectroscopic, calorimetric, computational, and cellular-based assays/methods. Results show that furosemide increases the lag phase and decreases the apparent rate of aggregation of human lysozyme, thereby decelerating the nucleation phase and amyloid fibril formation, as confirmed by the decrease in the level of Thioflavin-T fluorescence. Fewer entities of hydrodynamic radii of ∼171 nm instead of amyloid fibrils (∼412 nm) are detected in human lysozyme in the presence of furosemide by dynamic light scattering. Moreover, furosemide decreases the extent of conversion of the α/β structure of human lysozyme into a predominant β-sheet. The isothermal titration calorimetry established that furosemide forms a complex with human lysozyme, which was also confirmed through fluorescence quenching and computational studies. Also, human lysozyme lytic activity is inhibited competitively by furosemide due to the involvement of amino acid residues of the active site in catalysis, as well as complex formation. Conclusively, furosemide interacts with Gln58, Ile59, Asn60, Ala108, and Trp109 of aggregation-prone regions 2 and 4 of human lysozyme, thereby masking its sites of aggregation and generating only lowerorder entities that are less toxic to red blood cells than the fibrils. Thus, furosemide slows the progression of amyloid fibrillation in human lysozyme.

show abstract

Two polyphenols with diverse mechanisms towards amyloidosis: differential modulation of the fibrillation pathway of human lysozyme by curcumin and EGCG

Cited by 8 publications

References 65 publications

The effect of novel antihypertensive drug valsartan on lysozyme aggregation: A combined in situ and in silico study

The effect of novel antihypertensive drug valsartan on lysozyme aggregation: A combined in situ and in silico study

Effect of Antihypertensive Drug (Chlorothiazide) on Fibrillation of Lysozyme: A Combined Spectroscopy, Microscopy, and Computational Study

Furosemide Derails Human Lysozyme Fibrillation by Interacting with Aggregation Hot Spots: A Biophysical Comprehension

Contact Info

Product

Resources

About