Evidence mapPaperPMID 34976306Full record

ArticleComputational and structural biotechnology journal2021

Binding mode analysis of ABCA7 for the prediction of novel Alzheimer's disease therapeutics.

Vigneshwaran Namasivayam, Katja Stefan, Jens Pahnke, Sven Marcel Stefan

Open access · goldAbstract read
In one paragraph

Article in Computational and structural biotechnology journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.2field-weighted citation impact, top 18% 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

9 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. The ABC's of Alzheimer risk gene ABCA7.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
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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

4 authors at 2 institutions in 3 countries.

Vigneshwaran NamasivayamDepartment of Pharmaceutical and Cellbiological Chemistry, Pharmaceutical Institute, University of Bonn, An der Immenburg 4, 53121 Bonn, Germany.
Katja StefanDepartment of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab (www.pahnkelab.eu), University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway.
Jens PahnkeDepartment of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab (www.pahnkelab.eu), University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway.
Sven Marcel StefanDepartment of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab (www.pahnkelab.eu), University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway.
Oslo University Hospital · NOUniversity of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The adenosine-triphosphate-(ATP)-binding cassette (ABC) transporter ABCA7 is a genetic risk factor for Alzheimer's disease (AD). Defective ABCA7 promotes AD development and/or progression. Unfortunately, ABCA7 belongs to the group of 'under-studied' ABC transporters that cannot be addressed by small-molecules. However, such small-molecules would allow for the exploration of ABCA7 as pharmacological target for the development of new AD diagnostics and therapeutics. Pan-ABC transporter modulators inherit the potential to explore under-studied ABC transporters as novel pharmacological targets by potentially binding to the proposed 'multitarget binding site'. Using the recently reported cryogenic-electron microscopy (cryo-EM) structures of ABCA1 and ABCA4, a homology model of ABCA7 has been generated. A set of novel, diverse, and potent pan-ABC transporter inhibitors has been docked to this ABCA7 homology model for the discovery of the multitarget binding site. Subsequently, application of pharmacophore modelling identified the essential pharmacophore features of these compounds that may support the rational drug design of innovative diagnostics and therapeutics against AD.

Indexed as

ABC, ATP-binding cassetteABC transporter (ABCA1, ABCA4, ABCA7)AD, Alzheimer’s diseaseAlzheimer’s disease (AD)APP, amyloid precursor proteinATP, Adenosine-triphosphateBBB, blood-brain barrierBODIPY-cholesterol, 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene-cholesterolcryo-EM, cryogenic-electron microscopyECD, extracellular domainEH, extracellular helixGSH, reduced glutathioneHTS, high-throughput screeningIC, intracellular helixMOE, Molecular Operating EnvironmentMSD, membrane spanning domainMultitarget modulation (PANABC)NBD-cholesterol, 7-nitro-2-1,3-benzoxadiazol-4-yl-cholesterolNBD, nucleotide binding domainPDB, protein data bankPET, positron emission tomographyPET tracer (PETABC)PLIF, protein ligand interactionPolypharmacologyPSO, particle swarm optimizationRational drug design and developmentR-domain/region, regulatory domain/regionRMSD, root mean square distanceSNP, single-nucleotide polymorphismTM, transmembrane helix

Identifiers

PMID34976306
PMCPMC8666613
OpenAlexW3216702356

What Socratic holds

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LicenceCC BY
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.