Vescalagin and castalagin reduce the toxicity of amyloid-beta42 oligomers through the remodelling of its secondary structure

Araújo, Ana R.; Camero, Sergio; Taboada, Pablo; Reis, Rui L.

doi:10.1039/d0cc00192a

Cited by 7 publications

(10 citation statements)

References 23 publications

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“…32 These supramolecular arrangements can explain the lower MIC values for vescalagin toward methicillin-resistant bacteria ACS Biomaterials Science & Engineering pubs.acs.org/journal/abseba Letter as being due to its proven higher antiamyloidogenic capacity when compared with castalagin. 23,33 In the case of PA, the efficacy of CWE, CWE-E, and vescalagin/castalagin is lower. It is important to consider that PA is the only Gram-negative bacterium that we tested.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

“…In addition, some methicillin-resistant cell-wall-anchored proteins are composed by several connecting subdomains folded into β-sheet rich regions . These supramolecular arrangements can explain the lower MIC values for vescalagin toward methicillin-resistant bacteria as being due to its proven higher antiamyloidogenic capacity when compared with castalagin. , …”

Section: Resultsmentioning

confidence: 99%

“…In fact, we previously demonstrated that it is possible to extract a series of phenolic compounds using hot water, i.e., cork water extract (CWE), with important antioxidant activity . On the basis of these results, we also showed that it is possible to use CWE or vescalagin/castalagin (isolated from CWE) to protect DNA from UV-mediated damage and subsequent cell death, or as antiamyloidogenic agents …”

Section: Introductionmentioning

confidence: 97%

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Vescalagin and Castalagin Present Bactericidal Activity toward Methicillin-Resistant Bacteria

Araújo¹,

Reis²

2021

ACS Biomater. Sci. Eng.

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Polyphenols have been extensively exploited in the biomedical field because of their wide range of bioactive properties and historical use as traditional medicines. They typically present antioxidant, antimicrobial, antiamyloidogenic, and/or antitumor activities. In particular, cork water extracts and their components, have been previously reported to present antioxidant and antiamyloidogenic properties. On the basis of this knowledge, we tested cork water extract (CWE), cork water enriched extract (CWE-E), vescalagin/castalagin (two of the main polyphenols present in CWE and CWE-E) for their antibacterial activity against four bacterial strains, namely, methicillinresistant Staphylococcus epidermidis (MRSE), Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa (PA). Vescalagin and castalagin presented bactericidal activity against all the tested bacterial strains, in particular toward the methicillin-resistant ones, i.e., MRSA and MRSE, as well as the ability to inhibit the formation of biofilms and to disrupt preformed ones. Moreover, vescalagin/castalagin seem to modulate the normal assembly of the peptidoglycans at the bacteria surface, promoting the disruption of their cell wall, leading to bacterial cell death. We also demonstrate that vescalagin/castalagin can be loaded into alginate hydrogels to generate antibacterial biomaterials that are not toxic to eukaryotic cells.

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Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

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Vescalagin and Castalagin Present Bactericidal Activity toward Methicillin-Resistant Bacteria

Araújo¹,

Reis²

2021

ACS Biomater. Sci. Eng.

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“…Understanding the mechanistic determinants of amyloid-inhibitor interaction is a prerequisite for developing new drugs, as discussed in recent reviews, 193,831 and designing new strategies to reduce the toxicities by targeting Aβ, tau, αS and IAPP. 302,[832][833][834][835][836][837][838][839][840][841][842][843][844][845][846]…”

Section: Small Molecules Polymer-based Molecules and Carbon Nanoparticlesmentioning

confidence: 99%

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

et al. 2021

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Protein misfolding and aggregation is observed in many amyloidogenic diseases affecting either the central nervous system or a variety of peripheral tissues. Structural and dynamic characterization of all species along the pathways from monomers to fibrils is challenging by experimental and computational means because they involve intrinsically disordered proteins in most diseases. Yet understanding how amyloid species become toxic is the challenge in developing a treatment for these diseases. Here we review what computer, in vitro, in vivo and pharmacological experiments tell us about the accumulation and deposition of the oligomers of the (Aβ, tau), α-synuclein, IAPP and superoxide dismutase 1 proteins, which have been the mainstream concept underlying Alzheimer's disease (AD), Parkinson's disease (PD), type II diabetes (T2D) and amyotrophic lateral sclerosis (ALS) research, respectively for over many years.While SOD1 is a globular protein with a well-defined 3D structure, the Aβ, tau and α-synuclein proteins belong to the class of intrinsically disordered proteins (IDPs). IDPs are also known to play a critical role in many cellular functions such as signal transduction, cell growth, binding with DNA and RNA, and transcription, and are implicated in the development of cardiovascular problems and cancers 29 . The IDPs involved in neurodegenerative diseases have a few aggregation-prone regions and overall all IDPs have a low mean hydrophobicity and a high mean net charge 30 .IDPs are structurally flexible and lack stable secondary structures in aqueous solution. When isolated, they behave as polymers in a good solvent and their radii of gyration are well described by the Flory scaling law. 31 The insolubility and high self-assembly propensity of IDPs implicated in degenerative diseases have prevented high-resolution structural determination by solution nuclear magnetic resolution (NMR) and X-ray diffraction experiments. Local information at all aggregation steps can be, however, obtained by chemical shifts, residual coupling constants, and J-couplings from NMR, exchange hydrogen/deuterium (H/D) NMR, Raman spectroscopy; and secondary structure from fast Fourier infrared spectroscopy (FTIR) or circular dichroism (CD). Long-range tertiary contacts can be deduced from paramagnetic relaxation enhancement (PRE) NMR spectroscopy and single molecule Förster resonance energy transfer (sm-FRET), and short-range distance contacts can be extracted by cross linked residues determined by mass spectrometry (MS). Low-resolution 3D information of monomers and oligomers can be obtained by ion-mobility mass-spectrometry data (IM/MS) providing cross-collision sections, dynamic light scattering (DLS), pulse field gradient NMR spectroscopy and fluorescence correlation spectroscopy (FCS) providing hydrodynamics radius, small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS), atomic force microscopy (AFM) and transmission electron microscopy (TEM) providing height features of the aggregates, as reported by some o...

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“…Natural polyphenols (e.g., epigallocatechin gallate, 9 resveratrol, 10 or vescalagin 11 ) have been reported to remodel the supramolecular structure of amyloidogenic proteins/peptides. 12 They usually interfere with the H-bonding and hydrophobic interactions (e.g., π–π stacking) between the protein/peptide chains that are responsible for the stabilization of β-sheets present in the Aβ supramolecular species.…”

Section: Introductionmentioning

confidence: 99%

Functional Gallic Acid-Based Dendrimers as Synthetic Nanotools to Remodel Amyloid-β-42 into Noncytotoxic Forms

Araújo

Correa

Domínguez-Arca

et al. 2021

ACS Appl. Mater. Interfaces

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The self-assembly of amyloid-β (Aβ) generates cytotoxic oligomers linked to the onset and progression of Alzheimer’s disease (AD). As many fundamental molecular pathways that control Aβ aggregation are yet to be unraveled, an important strategy to control Aβ cytotoxicity is the development of bioactive synthetic nanotools capable of interacting with the heterogeneous ensemble of Aβ species and remodel them into noncytotoxic forms. Herein, the synthesis of nanosized, functional gallic acid (Ga)-based dendrimers with a precise number of Ga at their surface is described. It is shown that these Ga-terminated dendrimers interact by H-bonding with monomeric/oligomeric Aβ species at their Glu, Ala, and Asp residues, promoting their remodeling into noncytotoxic aggregates in a process controlled by the Ga units. The multivalent presentation of Ga on the dendrimer surface enhances their ability to interact with Aβ, inhibiting the primary and secondary nucleation of Aβ fibrillization and disrupting the Aβ preformed fibrils.

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Vescalagin and castalagin reduce the toxicity of amyloid-beta42 oligomers through the remodelling of its secondary structure

Cited by 7 publications

References 23 publications

Vescalagin and Castalagin Present Bactericidal Activity toward Methicillin-Resistant Bacteria

Vescalagin and Castalagin Present Bactericidal Activity toward Methicillin-Resistant Bacteria

Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer’s Disease, Parkinson’s Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis

Functional Gallic Acid-Based Dendrimers as Synthetic Nanotools to Remodel Amyloid-β-42 into Noncytotoxic Forms

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