Synaptic-Selective Autophagy Receptor Expression to Bypass Axonal Lysosome Deficiency
Curated pathway from expert analysis
flowchart TD
A["Axonal Lysosome<br/>Deficiency"]
B["Synaptic-Selective<br/>Autophagy Receptor"]
C["SQSTM1/p62 Binding<br/>to Ubiquitinated Cargo"]
D["Autophagosome<br/>Formation Bypassing soma"]
E["Synaptic Protein<br/>Clearance"]
F["Axonal Integrity<br/>Preserved"]
G["Bypasses Axonal<br/>Lysosome Deficit"]
A --> B
B --> C
C --> D
D --> E
E --> F
G -.->|"enables"| D
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style F fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for SQSTM1 yet. Search RCSB →
Median TPM across 13 brain regions for SQSTM1 (p62/sequestosome 1) 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 SQSTM1 (p62.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF SQSTM1 is selectively expressed in retinal ganglion cell axons using an AAV2 retrograde vector in a mouse model of axonal lysosome deficiency (PSEN1/APP triple knock-in), THEN axonal transport of s | Axonal transport velocity of synaptophysin-positive vesicles will increase by >30% (measured by in vivo imaging) and ERG photopic b-wave amplitude will normaliz | — no observation — | pending | 0.55 |
| IF synaptic-selective SQSTM1 (p62) is overexpressed via viral transduction in primary neurons with lysosome deficiency (LAMP2 knockdown), THEN synaptic protein ubiquitination will decrease by >40% mea | Synaptic protein ubiquitination will decrease by >40% (targeting known synaptic substrates like Synapsin I, PSD-95, and SV2A) | — no observation — | pending | 0.65 |