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Metabotropic glutamate receptor 5 (mGluR5) blockade ameliorates Huntington's disease pathology via activating convergent mechanisms of autophagy

2018· article· en· W3084342592 on OpenAlexaff
Khaled S. Abd‐Elrahman, Alison Hamilton, Shaunessy R. Hutchinson, Stephen S. G. Ferguson

Bibliographic record

VenueProceedings for Annual Meeting of The Japanese Pharmacological Society · 2018
Typearticle
Languageen
FieldNeuroscience
TopicGenetic Neurodegenerative Diseases
Canadian institutionsUniversity of Ottawa
Fundersnot available
KeywordsHuntingtinAutophagyMetabotropic glutamate receptor 5Huntington's diseaseGlutamate receptorMetabotropic glutamate receptorNeuroscienceDiseaseCell biologyMetabotropic glutamate receptor 1BlockadeMutantBiologyProtein aggregationChemistryMedicineReceptorPathologyGeneticsGeneApoptosis

Abstract

fetched live from OpenAlex

Background: Huntington´s disease (HD) is a neurodegenerative disorder that is characterized by progressive motor, cognitive and psychiatric impairments with no available disease modifying drugs. A mutant form of huntingtin protein that form aggregates is the underlying cause of HD. Genetic deletion of mGluR5 reduced disease pathology in Q111 knockin HD mouse model but the underlying mechanism of the observed reduction in aggregates was not described. Previous reports indicate that targeting autophagy proteins can reduces the formation of huntingtin aggregates. We tested whether the inhibition of mGluR5 will be effective in delaying the progression of HD by activating the autophagic removal of mutant huntingtin aggregates.

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 integrity0.0000.000
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 head0.024
GPT teacher head0.289
Teacher spread0.264 · 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

Citations0
Published2018
Admission routes1
Has abstractyes

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Same venueProceedings for Annual Meeting of The Japanese Pharmacological SocietySame topicGenetic Neurodegenerative DiseasesFrench-language works237,207