ID: hyp-SDA-2026-04-08-gap-debate-20260406-0
Hypothesis
Circadian Metabolic Reprogramming Therapy
Timed delivery of NAD+ precursors and AMPK activators to reset microglial circadian metabolism from glycolytic pro-inflammatory to oxidative anti-inflammatory phenotypes.
EvidencePending (0%)📖 5 cit🗣 1 debates✓ 5 support✗ 2 oppose
✓ All Quality Gates Passed
🧪 Overview
Timed delivery of NAD+ precursors and AMPK activators to reset microglial circadian metabolism from glycolytic pro-inflammatory to oxidative anti-inflammatory phenotypes
🧬 Mechanism
🧬 Curated Mechanism Pathway
Curated pathway from expert analysis
flowchart TD
A["Microglial Circadian Disruption<br/>Glycolytic Pro-Inflammatory Shift"]
B["NAD+ Depletion<br/>SIRT1 SIRT3 Activity Impaired"]
C["AMPK PRKAA1 Signaling Reduced<br/>Oxidative Metabolism Brake"]
D["Timed NAD+ Precursor Delivery<br/>NMN NR at Circadian Peak"]
E["AMPK Activator Administration<br/>AICAR Metformin at Trough"]
F["Sirtuin Reactivation<br/>SIRT1 Deacetylase Restored"]
G["PPARGC1A PGC1alpha Deacetylated<br/>Oxidative Phosphorylation Restored"]
H["Anti-Inflammatory Microglial Phenotype<br/>Homeostatic Circadian Metabolism"]
A --> B
A --> C
D --> F
E --> C
B --> F
C --> G
F --> G
G --> H
style G fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style H fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7⚖️ Evidence
⚖️ Evidence Matrix5 supports0 contradicts
Supports
Early glycolytic reprogramming controls microglial inflammatory activation.
Supports
SIRT1 activation by Ligustrazine ameliorates migraine via the paracrine interaction of microglia and neurons.
Supports
Paeoniflorin Inhibits the Activation of Microglia and Alleviates Depressive Behavior by Regulating SIRT1-NF-kB-NLRP3/Pyroptosis Pathway.
Supports
Huangqi Guizhi Wuwu decoction promotes M2 microglia polarization and synaptic plasticity via Sirt1/NF-κB/NLRP3 pathway in MCAO rats.
Supports
Alleviation of Microglia Mediating Hippocampal Neuron Impairments and Depression-Related Behaviors by Urolithin B via the SIRT1-FOXO1 Pathway.
📖 Linked Papers
No linked papers recorded for this hypothesis yet.
🏥 Translation
🧬 3D Protein Structure — SIRT1
💉 Clinical Trials
No clinical trials data linked to this hypothesis yet.
No curated ClinVar variants loaded for this hypothesis.
Run scripts/backfill_clinvar_variants.py to fetch P/LP/VUS variants.
No DepMap CRISPR Chronos data found for SIRT1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
🏆 Tournament
🏆 Arenas / Elo
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📊 Market Indicators
7d Trend
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Stable
7d Momentum
▲ 0.0%
Volatility
High
0.0535
Events (7d)
0
Price History
▲6.0%💾 Resource Usage
LLM Tokens
10,654
$0.0639
Total Cost
$0.0639
▸Metadatasource: v1_phase_c_backfill · origin_type: debate_synthesis
| source | v1_phase_c_backfill |
| origin_type | debate_synthesis |
| _schema_version | 1 |
📊 Evidence Profile
Evidence Balance
+0%
Certainty
0%
Debates
0
Incoming
0
Outgoing
0
0 supporting
0 contradicting
0 neutral
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