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Record W3039763043 · doi:10.1016/j.cellsig.2020.109704

Targeting AMP-activated protein kinase (AMPK) for treatment of autosomal dominant polycystic kidney disease

2020· review· en· W3039763043 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueCellular Signalling · 2020
Typereview
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic and Kidney Cyst Diseases
Canadian institutionsMcMaster UniversityUniversity of TorontoUniversity Health Network
FundersCanadian Institutes of Health Research
KeywordsAMPKmTORC1Autosomal dominant polycystic kidney diseaseMedicineProtein kinase AAMP-activated protein kinaseMitochondrial biogenesisEndocrinologyInternal medicineBiologyKidneyKinaseSignal transductionPI3K/AKT/mTOR pathwayCell biologyMitochondrion

Abstract

fetched live from OpenAlex

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenetic kidney disease worldwide and an important cause of chronic kidney disease. Multiple experimental studies have highlighted the role of increased mammalian target of rapamycin complex 1 (mTORC1) and reduced AMP-activated protein kinase (AMPK) signaling in modulating cyst growth in ADPKD. Notably, mTORC1 and AMPK are two diametrically opposing sensors of energy metabolism which regulate cell growth and proliferation. Although pharmacological mTORC1 inhibition was highly effective in experimental studies of ADPKD, clinical trials of mTORC1 inhibitors showed a lack of efficacy with low-dose treatment and poor tolerability with high-dose treatment. Therapeutic AMPK activation has been shown to attenuate cystic kidney disease severity in Pkd1 mutant animal models by improving mitochondrial biogenesis and reducing tissue inflammation. This review summarizes the current knowledge on the function of AMPK as a regulator of cellular energy metabolism and how AMPK activation by pharmacological and non-pharmacological means can potentially be exploited to treat ADPKD in the clinical settings.

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.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.848
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.001
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)0.0000.000

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 head0.027
GPT teacher head0.277
Teacher spread0.250 · 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