Evidence map›Paper›PMID 33865867›Full record

ArticleJournal of molecular biology2021

Degradation of Alzheimer's Amyloid-β by a Catalytically Inactive Insulin-Degrading Enzyme.

Bikash R Sahoo, Pritam Kumar Panda, Wenguang Liang, Wei-Jen Tang, Rajeev Ahuja, Ayyalusamy Ramamoorthy

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of molecular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

22 citing papers in PubMed, 42 citations in OpenAlex.

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  13. AβACS chemical neuroscience · 2023
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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 3 institutions in 2 countries.

Bikash R SahooBiophysics, Department of Chemistry, Macromolecular Engineering and Science, and Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Pritam Kumar PandaCondensed Matter Theory Group, Materials Theory Division, Department of Physics and Astronomy, Uppsala University, Box 516, SE-75120 Uppsala, Sweden.
Wenguang LiangBen-May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Wei-Jen TangBen-May Department for Cancer Research, The University of Chicago, Chicago, IL 60637, USA.
Rajeev AhujaCondensed Matter Theory Group, Materials Theory Division, Department of Physics and Astronomy, Uppsala University, Box 516, SE-75120 Uppsala, Sweden; Applied Materials Physics, Department of Materials Science and Engineering, Royal Institute of Technology (KTH) SE-10044 Stockholm, Sweden.
Ayyalusamy RamamoorthyBiophysics, Department of Chemistry, Macromolecular Engineering and Science, and Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: ramamoor@umich.edu.
University of Chicago · USUniversity of Michigan · USUppsala University · SE

Funding

Structure-function analysis and small molecule modulator discovery of human insulin degrading enzymeR01GM121964 · NIGMS · UNIVERSITY OF CHICAGO · PI TANG, WEI-JEN · 2017 to 2024
$3.1M
Membrane interaction and disruption by the Alzheimer's amyloid-beta peptideR01AG048934 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAMAMOORTHY, AYYALUSAMY · 2016 to 2020
$2.0M
NIA NIH HHS R01 AG048934NIGMS NIH HHS R01 GM121964
6 · The paper itself

Abstract

It is known that insulin-degrading-enzyme (IDE) plays a crucial role in the clearance of Alzheimer's amyloid-β (Aβ). The cysteine-free IDE mutant (cf-E111Q-IDE) is catalytically inactive against insulin, but its effect on Aβ degradation is unknown that would help in the allosteric modulation of the enzyme activity. Herein, the degradation of Aβ(1-40) by cf-E111Q-IDE via a non-chaperone mechanism is demonstrated by NMR and LC-MS, and the aggregation of fragmented peptides is characterized using fluorescence and electron microscopy. cf-E111Q-IDE presented a reduced effect on the aggregation kinetics of Aβ(1-40) when compared with the wild-type IDE. Whereas LC-MS and diffusion ordered NMR spectroscopy revealed the generation of Aβ fragments by both wild-type and cf-E111Q-IDE. The aggregation propensities and the difference in the morphological phenotype of the full-length Aβ(1-40) and its fragments are explained using multi-microseconds molecular dynamics simulations. Notably, our results reveal that zinc binding to Aβ(1-40) inactivates cf-E111Q-IDE's catalytic function, whereas zinc removal restores its function as evidenced from high-speed AFM, electron microscopy, chromatography, and NMR results. These findings emphasize the catalytic role of cf-E111Q-IDE on Aβ degradation and urge the development of zinc chelators as an alternative therapeutic strategy that switches on/off IDE's function.

Indexed as

Alzheimer DiseaseAmino Acid SequenceAmyloid beta-PeptidesBiocatalysisChromatography, High Pressure LiquidHumansInsulysinMass SpectrometryMicroscopy, Electron, TransmissionMolecular Dynamics SimulationMutant ProteinsMutation, MissensePeptide FragmentsProtein BindingProteolysisSubstrate SpecificityAmyloid beta-Peptidesamyloid beta-protein (1-40)InsulysinMutant ProteinsPeptide FragmentsZincAlzheimer's diseaseAmyloid-betaAmyloid degradationAβ(1–40)Insulin degrading enzyme

Identifiers

PMID33865867
PMCPMC8169600
OpenAlexW3155767338

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

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 Socratic graph.