Evidence map›Paper›PMID 25531836›Full record

ArticleBiochemistry2015

Mutational analysis of the ability of resveratrol to inhibit amyloid formation by islet amyloid polypeptide: critical evaluation of the importance of aromatic-inhibitor and histidine-inhibitor interactions.

Ling-Hsien Tu, Lydia M Young, Amy G Wong, Alison E Ashcroft, Sheena E Radford, Daniel P Raleigh

Abstract read
In one paragraph

Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 60 citations in OpenAlex.

  1. Review
  2. Review
  3. Mammals that can develop type 2 diabetes have a similarly structured β-sheet amyloid oligomer.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  15. Zinc boosts EGCG's hIAPP amyloid Inhibition both in solution and membrane.Biochimica et biophysica acta. Proteins and proteomics · 2019
    Article
  16. Review
  17. Review
  18. Natural product-based amyloid inhibitors.Biochemical pharmacology · 2017
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Ling-Hsien TuDepartment of Chemistry, Stony Brook University , Stony Brook, New York 11794-3400, United States.
Lydia M Young
Amy G Wong
Alison E Ashcroft
Sheena E Radford
Daniel P Raleigh
Stony Brook University · USUniversity of Leeds · GB

Funding

Biophysical Studies of Amyloid Formation by Polypeptide HormonesR01GM078114 · NIGMS · STATE UNIVERSITY NEW YORK STONY BROOK · PI RALEIGH, DANIEL P · 2008 to 2024
$5.1M
Biotechnology and Biological Sciences Research Council BB/E012558/1Biotechnology and Biological Sciences Research Council BB/I015361/1European Research Council 322408NIGMS NIH HHS GM078114NIGMS NIH HHS R01 GM078114
6 · The paper itself

Abstract

The process of amyloid formation by the normally soluble hormone islet amyloid polypeptide (IAPP) contributes to β-cell death in type 2 diabetes and in islet transplants. There are no clinically approved inhibitors of islet amyloidosis, and the mode of action of existing inhibitors is not well-understood. Resveratrol, a natural polyphenol, has been reported to inhibit amyloid formation by IAPP and by the Alzheimer's disease Aβ peptide. The mechanism of action of this compound is not known, nor is its mode of interaction with IAPP. In this study, we use a series of IAPP variants to examine possible interactions between resveratrol and IAPP. Fluorescence assays, transmission electron microscopy, and mass spectrometry demonstrate that resveratrol is much less effective as an inhibitor of IAPP amyloid formation than the polyphenol (-)-epigallocatechin 3-gallate (EGCG) and, unlike EGCG, does not significantly disaggregate preformed IAPP amyloid fibrils. Resveratrol is also shown to interfere with thioflavin-T assays. His-18 mutants, a truncation mutant, mutants of each of the aromatic residues, and mutants of Arg-11 of IAPP were examined. Mutation of His to Gln or Leu weakens the ability of resveratrol to inhibit amyloid formation by IAPP, as do mutations of Arg-11, Phe-15, or Tyr-37 to Leu, and truncation to form the variant Ac 8-37-IAPP, which removes the first seven residues to eliminate Lys-1 and the N-terminal amino group. In contrast, replacement of Phe-23 with Leu has a smaller effect. The data highlight Phe-15, His-18, and Tyr-37 as being important for IAPP-resveratrol interactions and are consistent with a potential role of the N-terminus and Arg-11 in polypeptide-resveratrol interactions.

Indexed as

Amino Acids, AromaticAmino Acid SequenceAmyloidArginineBenzothiazolesCatechinDNA Mutational AnalysisHistidineHumansIslet Amyloid PolypeptideMolecular Sequence DataMutant ProteinsResveratrolSpectrometry, Mass, Electrospray IonizationStilbenesStructure-Activity RelationshipAmino Acids, AromaticAmyloidArginineBenzothiazolesCatechinepigallocatechin gallateHistidineIslet Amyloid PolypeptideMutant ProteinsResveratrolStilbenesThiazolesthioflavin T

Identifiers

PMID25531836
PMCPMC4310630
OpenAlexW2011192333

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.