Evidence map›Paper›PMID 39352120›Full record

ArticleDisease models & mechanisms2024

Activation of the heat shock response as a therapeutic strategy for tau toxicity.

Taylor R Stanley, Elizabeth M Otero, Amy L Knight, Aleen D Saxton, Xinxing Ding, Melissa Borgen, Brian C Kraemer, Karen S Kim Guisbert, Eric Guisbert

Abstract read
In one paragraph

Article in Disease models & mechanisms, 2024. 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
–field-weighted citation impact
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.

  1. Review
  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.

Taylor R StanleyBiomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
Elizabeth M OteroBiomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
Amy L KnightBiomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
Aleen D SaxtonGeriatrics Research Education and Clinical Center (GRECC), Veterans Affairs Puget Sound Healthcare System, 1660 South Columbian Way Seattle, WA 98108-1532, USA.
Xinxing DingBiomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
Melissa BorgenBiomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
Brian C KraemerGeriatrics Research Education and Clinical Center (GRECC), Veterans Affairs Puget Sound Healthcare System, 1660 South Columbian Way Seattle, WA 98108-1532, USA.ORCID 0000-0002-2252-7634
Karen S Kim GuisbertBiomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.
Eric GuisbertBiomedical Sciences Program, Florida Institute of Technology, Melbourne, Florida.ORCID 0000-0003-1901-5598

Funding

University of Washington Alzheimer's Disease Research CenterP30AG066509 · NIA · UNIVERSITY OF WASHINGTON · PI Amanda D. Boyd · 2020 to 2026
$29.0M
Enhancing and expanding the CGC Strain CollectionP40OD010440 · OD · UNIVERSITY OF MINNESOTA · PI Aric L Daul, Ann E. Rougvie · 2012 to 2026
$7.5M
Regulatory mechanisms linking HSF1 protein levels and HSF1 protein activity to the alternative splicing factor SF3B1R15CA227573 · NCI · FLORIDA INSTITUTE OF TECHNOLOGY · PI GUISBERT, ERIC · 2019 to 2019
$430k
Community Foundation for BrevardNCI NIH HHS R15 CA227573NIA NIH HHS P30 AG066509NIH HHS P40 OD010440University of Nebraska Omaha
6 · The paper itself

Abstract

Alzheimer's disease is associated with the misfolding and aggregation of two distinct proteins, beta-amyloid and tau. Previously, it has been shown that activation of the cytoprotective heat shock response (HSR) pathway reduces beta-amyloid toxicity. Here, we show that activation of the HSR is also protective against tau toxicity in a cell-autonomous manner. Overexpression of HSF-1, the master regulator of the HSR, ameliorates the motility defect and increases the lifespan of transgenic C. elegans expressing human tau. By contrast, RNA interference of HSF-1 exacerbates the motility defect and shortens lifespan. Targeting regulators of the HSR also affects tau toxicity. Additionally, two small-molecule activators of the HSR, Geranylgeranylacetone (GGA) and Arimoclomol (AC), have substantial beneficial effects. Taken together, this research expands the therapeutic potential of HSR manipulation to tauopathies and reveals that the HSR can impact both beta-amyloid and tau proteotoxicity in Alzheimer's disease.

Indexed as

Alzheimer DiseaseCaenorhabditis elegansHeat-Shock ResponseAmyloid beta-PeptidesAnimalsAnimals, Genetically ModifiedCaenorhabditis elegans ProteinsDiterpenesHumansLongevitytau ProteinsTranscription FactorsAmyloid beta-PeptidesCaenorhabditis elegans ProteinsDiterpenesgeranylgeranylacetoneheat shock factor-1, C eleganstau ProteinsTranscription FactorsAlzheimer’s diseaseCaenorhabditis elegansHeat shock responseHSF1Tau (MAPT)

Identifiers

PMID39352120
PMCPMC11463952

What Socratic holds

Textmetadata
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.