Hsp70 cochaperone BAG3-mediated Autophagy Activation for Synaptic Protein Quality Control
Curated pathway from expert analysis
flowchart TD
A["Synaptic Protein Misfolding<br/>Age-related aggregation"]
B["Hsc70 Chaperone<br/>Client Substrate Binding"]
C["BAG3 Cochaperone<br/>Hsc70 ATPase regulation"]
D["p62/SQSTM1 Bridging<br/>Autophagy receptor recruitment"]
E["LC3-II Interaction<br/>Autophagosome membrane"]
F["Selective Macroautophagy<br/>Chaperone-assisted"]
G["Lysosomal Degradation<br/>Aggregate clearance"]
H["Synaptic Proteostasis<br/>Neuroprotection"]
A --> B
B --> C
C --> D
D --> E
E --> F
F --> G
G --> H
style C fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style H fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for BAG3 yet. Search RCSB →
Median TPM across 13 brain regions for BAG3 (Bcl-2-associated athanogene 3) 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 BAG3 (Bcl-2-associated athanogene 3).
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF BAG3 is selectively overexpressed at synapses using AAV9-Synapsin-BAG3-mCherry stereotactically injected into bilateral hippocampus of 3xTg-AD mice at 6 months of age, THEN synaptic autophagy marke | Expected ≥50% increase in synaptic LC3-II/LC3-I ratio and ≥35% reduction in synaptic AT8 (pS202/pT208) signal normalized to synaptic PSD-95 in BAG3-overexpressi | — no observation — | pending | 0.58 |
| IF BAG3 is knocked down in mature hippocampal neurons (DIV14) via lentiviral CRISPR/Cas9 editing targeting BAG3 exons 2-3, THEN synaptic autophagy flux will be significantly reduced (measured by decre | Expected ≥40% reduction in synaptic LC3-II puncta per bassoon-positive terminal and ≥30% increase in synaptic ubiquitin signal density compared to scrambled gui | — no observation — | pending | 0.67 |