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Record W1420881027 · doi:10.3233/jad-140348

Modulation of Amyloid-β Protein Precursor Expression by HspB1

2014· article· en· W1420881027 on OpenAlexafffund
Megan Conway, Firoozeh Nafar, Tatjana Straka, Karen M. Mearow

Bibliographic record

VenueJournal of Alzheimer s Disease · 2014
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicHeat shock proteins research
Canadian institutionsMemorial University of Newfoundland
FundersCanadian Institutes of Health Research
KeywordsHsp27Hsp70Heat shock proteinCell cultureCell biologyChemistryDownregulation and upregulationHEK 293 cellsAmyloid precursor proteinAmyloid (mycology)Molecular biologyBiochemistryAlzheimer's diseaseBiologyDiseaseMedicineGeneticsInternal medicineGene

Abstract

fetched live from OpenAlex

Upregulation of heat shock proteins, such as Hsp70 and HspB1/Hsp27, have been associated with an amelioration of the deficits in animal models of Alzheimer's disease (AD). HspB1 is reported to be increased in AD brains and to accumulate in plaques, but whether this localization is an attempt by HspB1 to ameliorate the detrimental effects of amyloid-β (Aβ) on cells or part of the disease process is unknown. Here we explore the potential effects of the HspB1 on amyloid-β protein precursor (AβPP) processing and distribution within HEK293 stable cell lines expressing either AβPPwt or AβPPsw. We compare AβPP production, distribution, and release of proteolytic products (including Aβ40 and Aβ42) to determine possible modifications in the presence of HspB1. We also investigate whether HspB1 interacts with Aβ or its precursor, AβPP, and whether, through this interaction, it is able to alter AβPP processing or release of Aβ peptide. Coexpression of HspB1 resulted in increased cellular holoAβPP as well as C-terminal fragments. Further, expression of HspB1 attenuated the release of Aβ42 from the AβPPsw cells. In summary, we have shown that expression of HspB1 alters AβPP expression and processing in cell lines expressing AβPPwt and AβPPsw. Furthermore, the presence of HspB1 decreased the amount of Aβ42 released by the cell lines. Thus in addition to its effects on protecting cells from the potentially toxic effects of Aβ, HspB1 also appears to be involved in modulating cellular levels of AβPP, although an understanding of the underlying mechanisms requires further investigation.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.004

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.015
GPT teacher head0.287
Teacher spread0.272 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations20
Published2014
Admission routes2
Has abstractyes

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