Astrocyte-Neuron Lactate Shuttle Enhancement via Pharmacological Activation of Monocarboxylate Transporters
Curated pathway from expert analysis
flowchart TD
A["SLC16A3/MCT4<br/>Monocarboxylate Transporter"]
B["Astrocyte-Neuron<br/>Lactate Shuttle"]
C["Lactate as<br/>Energy Substrate"]
D["Neuronal Metabolic<br/>Support"]
E["Astrocyte-Neuron<br/>Metabolic Coupling"]
F["Neuroenergetic<br/>Resilience"]
G["MCT4 Activation<br/>as Metabolic Enhancer"]
A --> B
B --> C
C --> D
D --> E
E --> F
G -.->|"facilitates"| B
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for SLC16A3 yet. Search RCSB →
Median TPM across 13 brain regions for SLC16A3 (MCT4) from GTEx v10.
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 SLC16A3 (MCT4).
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF C57BL/6 mice subjected to transient middle cerebral artery occlusion (tMCAO) receive chronic MCT4 activator treatment (10 mg/kg/day i.p.) for 14 days post-infarction, THEN motor function will impro | 30% improvement in motor coordination (rotarod latency) and normalization of striatal lactate levels to near-sham baseline, indicating restored ANLS functionali | — no observation — | pending | 0.55 |
| IF primary mouse astrocyte-neuron co-cultures are treated with a selective MCT4 agonist (10 μM, 24h), THEN extracellular lactate in the astrocyte compartment will decrease by ≥20% AND neuronal NAD+/NA | Reduced extracellular lactate in astrocyte compartment (≥20% decrease) and elevated neuronal NAD+/NADH ratio (≥15% increase), indicating enhanced lactate shuttl | — no observation — | pending | 0.65 |