Understanding curcumin-induced modulation of protein aggregation

Ahmad, Basir; Borana, Mohanish; Chaudhary, Ankur P.

doi:10.1016/j.ijbiomac.2016.06.053

Cited by 31 publications

(24 citation statements)

References 67 publications

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“…It is important to understand the mechanism of aggregation/fibrillation prevention and to design suitable inhibitors. The process of HSA fibrillation has been well documented [20][21][22][23][24][25][26][27][28]. Fibrillar aggregates (amyloid fibrils, protein fibrils) are insoluble and heterogenous, characterized by a cross-stretched β-structure and the ability to bind dyes such as thioflavin T (ThT) and Congo red.…”

Section: Introductionmentioning

confidence: 99%

Human Serum Albumin Aggregation/Fibrillation and its Abilities to Drugs Binding

et al. 2020

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Human serum albumin (HSA) is a protein that transports neutral and acid ligands in the organism. Depending on the environment’s pH conditions, HSA can take one of the five isomeric forms that change its conformation. HSA can form aggregates resembling those in vitro formed from amyloid at physiological pH (neutral and acidic). Not surprisingly, the main goal of the research was aggregation/fibrillation of HSA, the study of the physicochemical properties of formed amyloid fibrils using thioflavin T (ThT) and the analysis of ligand binding to aggregated/fibrillated albumin in the presence of dansyl-l-glutamine (dGlu), dansyl-l-proline (dPro), phenylbutazone (Phb) and ketoprofen (Ket). Solutions of human serum albumin, both non-modified and modified, were examined with the use of fluorescence, absorption and circular dichroism (CD) spectroscopy. The experiments conducted allowed observation of changes in the structure of incubated HSA (HSAINC) in relation to nonmodified HSA (HSAFR). The formed aggregates/fibrillation differed in structure from HSA monomers and dimers. Based on CD spectroscopy, previously absent β-structural constructs have been registered. Whereas, using fluorescence spectroscopy, the association constants differing for fresh and incubated HSA solutions in the presence of dansyl-amino acids and markers for binding sites were calculated and allowed observation of the conformational changes in HSA molecule.

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Section: Introductionmentioning

confidence: 99%

Human Serum Albumin Aggregation/Fibrillation and its Abilities to Drugs Binding

et al. 2020

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“…This effect could be associated with the reduction in intracellular HSP60 levels and its release in the extracellular space. Moreover, it is well known that curcumin presents an anti-aggregation effect in a different class of proteins by modulating their conformational stability and unfolding/folding pathways [27]. Concerning the effect on HSP60, we…”

Section: Discussionmentioning

confidence: 90%

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

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et al. 2020

IJMS

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The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial–mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of protein homeostasis and cell survival. High HSP60 levels were correlated, in particular, with cancer development and progression, and for this reason, we investigated the ability of curcumin to affect HSP60 expression, localization, and post-translational modifications using a neuroblastoma cell line. We have also looked at the ability of curcumin to interfere with the HSP60/HSP10 folding machinery. The cells were treated with 6, 12.5, and 25 µM of curcumin for 24 h, and the flow cytometry analysis showed that the compound induced apoptosis in a dose-dependent manner with a higher percentage of apoptotic cells at 25 µM. This dose of curcumin-induced a decrease in HSP60 protein levels and an upregulation of HSP60 mRNA expression. Moreover, 25 µM of curcumin reduced HSP60 ubiquitination and nitration, and the chaperonin levels were higher in the culture media compared with the untreated cells. Furthermore, curcumin at the same dose was able to favor HSP60 folding activity. The reduction of HSP60 levels, together with the increase in its folding activity and the secretion in the media led to the supposition that curcumin might interfere with cancer progression with a protective mechanism involving the chaperonin.

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“…In this study we report a lack of chemical shift changes following addition of 4,454 W to aSyn showing 4554W doesn’t associate with monomeric asyn. The flavonoid epigallocatechin gallate and phenol curcumin have shown potential for inhibiting several aggregation-prone proteins ( Ehrnhoefer et al, 2008 ; Ahmad et al, 2017 ). They also act via direct association to prevent the structural re-arrangement required for fibril formation ( Meng et al, 2009 ; Takahashi et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Insights Into Peptide Inhibition of Alpha-Synuclein Aggregation

et al. 2020

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α-Synuclein (aSyn) aggregation is an attractive target for therapeutic development for a range of neurodegenerative conditions, collectively termed synucleinopathies. Here, we probe the mechanism of action of a peptide 4554W, (KDGIVNGVKA), previously identified through intracellular library screening, to prevent aSyn aggregation and associated toxicity. We utilize NMR to probe association and identify that 4554W associates with a “partially aggregated” form of aSyn, with enhanced association occurring over time. We also report the ability of 4554W to undergo modification through deamidation of the central asparagine residue, occurring on the same timescale as aSyn aggregation in vitro , with peptide modification enhancing its association with aSyn. Additionally, we report that 4554W can act to reduce fibril formation of five Parkinson’s disease associated aSyn mutants. Inhibitory peptide binding to partially aggregated forms of aSyn, as identified here, is particularly attractive from a therapeutic perspective, as it would eliminate the need to administer the therapy at pre-aggregation stages, which are difficult to diagnose. Taken together the data suggest that 4554W could be a suitable candidate for future therapeutic development against wild-type, and most mutant aSyn aggregation.

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Understanding curcumin-induced modulation of protein aggregation

Cited by 31 publications

References 67 publications

Human Serum Albumin Aggregation/Fibrillation and its Abilities to Drugs Binding

Human Serum Albumin Aggregation/Fibrillation and its Abilities to Drugs Binding

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Insights Into Peptide Inhibition of Alpha-Synuclein Aggregation

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