Morin hydrate inhibits amyloid formation by islet amyloid polypeptide and disaggregates amyloid fibers

Noor, Harris; Cao, Ping; Raleigh, Daniel P.

doi:10.1002/pro.2023

Cited by 115 publications

(98 citation statements)

References 51 publications

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“…Quercetin and myricetin efficacy as amyloid aggregation inhibitors and preformed fibril destabilizers was confirmed with insulin and α-syn, respectively [262,263]; yet, other compelling results were also reported: Jagota et al [264] suggested that quercetin inhibits Aβ fibrillization, but not its toxic oligomerization, hence increasing Aβ toxicity in a C. elegans model of Aβ deposition; Noor et al [265] reported that quercetin and myricetin were not able to prevent hIAPP fibrillation, at variance with morin (which differs only for the position and/or the number of the hydroxyl groups on the B ring). However, they did not investigate the possible effects of the two flavonols either on the most harmful oligomeric species or on aggregate toxicity.…”

Section: The Anti-amyloid Properties Of Natural Phenols and Polyphmentioning

confidence: 99%

“…The array of natural phenols being tested as potential inhibitors of amyloid aggregation becomes wider and wider every day and now includes also tannic acid [207,313] and the product of tannin hydrolysis ellagic acid [314]; several flavones, like apigenin [315,316], baicalein [315,317,318], kaempferol [260,261,263,264,271,319], morin [265,320,321], fisetin [259,260,321], rutin (the glycoside of quercetin with the disaccharide rutinose) [322,323] and luteolin [260,324]; rottlerin, already known as a PKC-δ inhibitor [325,326]; the anthocyanidin malvidin, the main responsible for the red color of wine [327]; the stilbenes piceatannol [328] and the resveratrol-derived dimer ɛ-viniferin glucoside [329]; and, finally, ferulic acid (related to trans-cinnamic acid) [189,263,264,330–332]. …”

Section: The Anti-amyloid Properties Of Natural Phenols and Polyphmentioning

confidence: 99%

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Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds

Stefani

Rigacci

2013

IJMS

192

127

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Amyloid aggregation is a hallmark of several degenerative diseases affecting the brain or peripheral tissues, whose intermediates (oligomers, protofibrils) and final mature fibrils display different toxicity. Consequently, compounds counteracting amyloid aggregation have been investigated for their ability (i) to stabilize toxic amyloid precursors; (ii) to prevent the growth of toxic oligomers or speed that of fibrils; (iii) to inhibit fibril growth and deposition; (iv) to disassemble preformed fibrils; and (v) to favor amyloid clearance. Natural phenols, a wide panel of plant molecules, are one of the most actively investigated categories of potential amyloid inhibitors. They are considered responsible for the beneficial effects of several traditional diets being present in green tea, extra virgin olive oil, red wine, spices, berries and aromatic herbs. Accordingly, it has been proposed that some natural phenols could be exploited to prevent and to treat amyloid diseases, and recent studies have provided significant information on their ability to inhibit peptide/protein aggregation in various ways and to stimulate cell defenses, leading to identify shared or specific mechanisms. In the first part of this review, we will overview the significance and mechanisms of amyloid aggregation and aggregate toxicity; then, we will summarize the recent achievements on protection against amyloid diseases by many natural phenols.

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Section: The Anti-amyloid Properties Of Natural Phenols and Polyphmentioning

confidence: 99%

Section: The Anti-amyloid Properties Of Natural Phenols and Polyphmentioning

confidence: 99%

Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds

Stefani

Rigacci

2013

IJMS

192

127

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“…The search for inhibitors of amyloid fiber formation is an active area of research and particular attention has been focused on flavanols (4–15). Among the most potent inhibitors found to date is the ester of epigallocatechin and gallic acid, (−)-Epigallocatechin 3-Gallate [EGCG; (2 R ,3 R )-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2 H -1-benzopyran-3-yl 3,4,5-trihydroxybenzoate].…”

mentioning

confidence: 99%

Analysis of the Inhibition and Remodeling of Islet Amyloid Polypeptide Amyloid Fibers by Flavanols

2012

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Islet amyloid polypeptide (IAPP, amylin) is responsible for amyloid formation in type 2 diabetes and in transplanted islets. The flavanol, (−)-Epigallocatechin-3-gallate [EGCG; (2R,3R)-5,7-dihydroxy-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-2H-1-benzopyran-3-yl3,4,5-trihydroxybenzoate] is an effective inhibitor of amyloid formation by IAPP, however, the interactions required for the inhibition of IAPP amyloid formation and for the remodeling of amyloid fibers are not known. A range of features have been proposed to be critical for EGCG protein interactions, including interactions with aromatic residues, interactions with amino groups, or sulfhydryls. Using a set of IAPP analogs we show that none of these are required. Studies in which EGCG is added to the lag phase of amyloid formation suggest that it interacts with intermediates as well as with monomers and amyloid. The features of EGCG required for effective inhibition were examined. The stereoisomer of EGCG, (−)-Gallocatechin gallate (GCG), is an effective inhibitor, although less so than EGCG. Removing the gallate ester moiety leads to EGC which is a less effective inhibitor. Removing only the 3-hydroxyl group of the tri-hydroxyphenyl ring leads to a compound which has more pronounced effects on the lag phase than EGC, but is less effective at reducing the amount of amyloid. Elimination of both the 3-hydroxy group and the gallate ester results in loss of activity. EGCG remodels IAPP amyloid fibers, but does not fully resolubilize them to unstructured monomers and the remodeling is not the reverse of amyloid assembly. The ability of the compounds to remodel IAPP amyloid closely follows their relative ability to inhibit amyloid formation.

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“…The search for inhibitors of amyloid aggregation and amyloid formation is an active area of research, 10−17 but comparatively few anti-amylin amyloid compounds have been developed, and the vast majority of those are not drug-like. Recently, the intriguing possibility that clinically relevant doses of aspirin and the nonsteroid anti-inflammatory drug (NSAID) ketoprofen may inhibit amylin amyloid formation and might disaggregate preformed amylin amyloid fibrils has been raised.…”

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confidence: 99%

Aspirin, Diabetes, and Amyloid: Re-examination of the Inhibition of Amyloid Formation by Aspirin and Ketoprofen

Noor

Cao

et al. 2014

ACS Chem. Biol.

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The loss of β-cell function and β-cell death are key features of diabetes. A range of mechanisms are thought to contribute to β-cell loss, including islet amyloid formation by the neuropancreatic hormone amylin (islet amyloid polypeptide, IAPP). Islet amyloid deposition also contributes to the failure of islet transplants. There are no therapeutic strategies for the treatment or prevention of islet amyloidosis. Aspirin and the nonsteroid anti-inflammatory drug (NSAID) ketoprofen, at clinically relevant doses, have been proposed to inhibit amyloid formation by amylin and thus may hold promise for treatment of islet amyloidosis. These compounds are potentially attractive given the importance of inflammation in islet amyloidosis and given the fact that there are no anti-islet amyloid agents in the clinic. We show that aspirin, even in 20-fold excess, has no effect on the kinetics of amyloid formation by amylin as judged by thioflavin-T binding, right angle light scattering, and transmission electron microscopy, nor does it alter the morphology of resulting amyloid fibrils. Aspirin showed no ability to disaggregate preformed amylin amyloid fibrils under the conditions of these studies, 25 °C and pH 7.4. Ketoprofen is similarly ineffective at inhibiting amylin amyloid formation. The compounds do, however, interfere with circular dichroism- and Congo Red-based assays of amylin amyloid formation. This study highlights the importance of using multiple methods to follow amyloid formation when screening inhibitors.

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Morin hydrate inhibits amyloid formation by islet amyloid polypeptide and disaggregates amyloid fibers

Cited by 115 publications

References 51 publications

Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds

Protein Folding and Aggregation into Amyloid: The Interference by Natural Phenolic Compounds

Analysis of the Inhibition and Remodeling of Islet Amyloid Polypeptide Amyloid Fibers by Flavanols

Aspirin, Diabetes, and Amyloid: Re-examination of the Inhibition of Amyloid Formation by Aspirin and Ketoprofen

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