Evidence map›Paper›PMID 34954854›Full record

ArticleProtein science : a publication of the Protein Society2022

Atomic view of an amyloid dodecamer exhibiting selective cellular toxic vulnerability in acute brain slices.

Amber L H Gray, Michael R Sawaya, Debalina Acharyya, Jinchao Lou, Emery M Edington, Michael D Best, Rebecca A Prosser, David S Eisenberg, Thanh D Do

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

Article in Protein science : a publication of the Protein Society, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
1.2field-weighted citation impact, top 21% 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

2 citing papers in PubMed, 14 citations in OpenAlex.

  1. Article
  2. 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

9 authors at 2 institutions in 1 country.

Amber L H GrayDepartment of Chemistry, University of Tennessee, Knoxville, Tennessee, USA.
Michael R SawayaHHMI, University of California, Los Angeles, California, USA.
Debalina AcharyyaDepartment of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, USA.
Jinchao LouDepartment of Chemistry, University of Tennessee, Knoxville, Tennessee, USA.
Emery M EdingtonDepartment of Chemistry, University of Tennessee, Knoxville, Tennessee, USA.
Michael D BestDepartment of Chemistry, University of Tennessee, Knoxville, Tennessee, USA.
Rebecca A ProsserDepartment of Biochemistry & Cellular and Molecular Biology, University of Tennessee, Knoxville, Tennessee, USA.
David S EisenbergHHMI, University of California, Los Angeles, California, USA.
Thanh D DoDepartment of Chemistry, University of Tennessee, Knoxville, Tennessee, USA.ORCID 0000-0002-1978-4365
University of Tennessee at Knoxville · USUniversity of California, Los Angeles · US

Funding

Towards Treatment of Alzheimer’s Disease by Targeting Pathogenic Tau and Beta-Amyloid StructuresR01AG070895 · NIA · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DAVID EISENBERG · 2022 to 2026
$5.8M
NIA NIH HHS R01 AG070895
6 · The paper itself

Abstract

Atomic structures of amyloid oligomers that capture the neurodegenerative disease pathology are essential to understand disease-state causes and finding cures. Here we investigate the G6W mutation of the cytotoxic, hexameric amyloid model KV11. The mutation results into an asymmetric dodecamer composed of a pair of 30° twisted antiparallel β-sheets. The complete break between adjacent β-strands is unprecedented among amyloid fibril crystal structures and supports that our structure is an oligomer. The poor shape complementarity between mated sheets reveals an interior channel for binding lipids, suggesting that the toxicity may be due to a perturbation of lipid transport rather than a direct disruption of membrane integrity. Viability assays on mouse suprachiasmatic nucleus, anterior hypothalamus, and cerebral cortex demonstrated selective regional vulnerability consistent with Alzheimer's disease. Neuropeptides released from the brain slices may provide clues to how G6W initiates cellular injury.

Indexed as

Alzheimer DiseaseNeurodegenerative DiseasesAmyloidAmyloid beta-PeptidesAnimalsBrainMiceModels, MolecularPeptide FragmentsAmyloidAmyloid beta-PeptidesPeptide Fragmentsamyloid oligomersbrain slicesion-mobility mass spectrometrysuprachiasmatic nucleusX-ray crystallography

Identifiers

PMID34954854
PMCPMC8862425
OpenAlexW4200050574

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.