HIF-1 plays a dual regulatory role in hippocampal neuronal PANoptosis in Alzheimer's disease via the HK2/VDAC1/NLRP3 axis and RIPK3 signaling
- Design
- Animal study · Unknown outcome
- Match to healthy normal-weight adults aged 55–75
- Not human evidence[Auto] Non-human (animal or cellular) evidence; no direct inference to any human population.
- Could weight loss explain it?
- Unknown[Auto] Non-human study; weight-loss mediation not assessable.
- Study tier
- Study tier 4[Auto] Preclinical evidence; not clinical evidence for any human population.
- Assessment
- Version 1 · automatic, not yet reviewed by a person · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
[Auto, unreviewed; last sentences of abstract] Finally, we uncovered that semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), mitigates hippocampal neuronal PANoptosis by reprograming the double-eged sword effect of HIF-1 mediated by GLP-1R-AMPK signaling pathway, highlighting its potential as a therapeutic avenue for AD. These findings uncover a previously unrecognized role of PANoptosis in AD and provide new insights into the HIF-1-mediated regulatory mechanisms, offering a promising target for therapeutic intervention.
01Findings
What the study reported
- Drugs
- Semaglutide
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- Not stated
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Baseline condition
- Alzheimer's disease / MCI
Study quality details
- Study design
- Preclinical (animal)
- Sample size
- not extracted
- Randomization
- no
- Blinding
- not stated
- Comparator
- not stated
- Follow up duration
- not stated
- Outcome type
- unknown
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- VERY_INDIRECT
- Statistical precision
- not extracted
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- not reported in abstract
- Industry funded
- Unclear
- Manufacturer
- None identified
- Sponsor role
- not reported in abstract
- Author conflicts
- Declaration of Competing Interest The authors declare no competing interests.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
Extensive neuronal loss in brain regions critical for learning and memory is a hallmark of Alzheimer's disease (AD). PANoptosis, a newly characterized form of programmed cell death, integrates the key features of pyroptosis, apoptosis and necroptosis, and explains the molecular crosstalk among these pathways. However, whether PANoptosis is a new manner for hippocampal neuron death in AD, and the involved regulatory mechanisms remains largely unknown. Here, we demonstrate that PANoptosis is a crucial mechanism driving hippocampal neuronal loss in an AD mouse model. Moreover, we uncovered that the HIF-1 signaling pathway exerts a double-edged sword effect on hippocampal neuronal PANoptosis by activating the HK2/VDAC1/NLRP3 axis while concurrently suppressing RIPK3 signal. This observation may offer a partial explanation for the double-edged sword role of HIF-1 as both a neuroprotective and neurotoxic factor in AD. Finally, we uncovered that semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), mitigates hippocampal neuronal PANoptosis by reprograming the double-eged sword effect of HIF-1 mediated by GLP-1R-AMPK signaling pathway, highlighting its potential as a therapeutic avenue for AD. These findings uncover a previously unrecognized role of PANoptosis in AD and provide new insights into the HIF-1-mediated regulatory mechanisms, offering a promising target for therapeutic intervention.
Where this record came from
| Source | Retrieved | Identifier |
|---|---|---|
| pubmed | Sep 13, 2026 | 42702341 first ingestion |