Cathepsin D Replacement to Overcome Lysosomal Protease Deficiency
Curated pathway from expert analysis
flowchart TD
A["Cathepsin D<br/>Protease Deficiency"]
B["Lysosomal<br/>Proteolysis Impairment"]
C["Accumulated<br/>Substrate Proteins"]
D["Proteostasis<br/>Failure"]
E["Exogenous Cathepsin D<br/>Replacement"]
F["Lysosomal<br/>Function Restoration"]
G["Proteostatic<br/>Recovery"]
A --> B
B --> C
C --> D
E --> F
F --> G
G --> D
style A fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
style G fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for CTSD yet. Search RCSB →
Median TPM across 13 brain regions for CTSD (cathepsin D) 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 CTSD (cathepsin D).
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF cultured CTSD-deficient patient-derived fibroblasts are treated with exogenous recombinant human cathepsin D enzyme (50 μg/mL, 72 hours), THEN intracellular lysosomal autofluorescence (lipofuscin a | ≥40% reduction in lysosomal autofluorescence intensity and restoration of cathepsin D activity to ≥25% of normal levels | — no observation — | pending | 0.00 |
| IF CTSD-knockout mice (Ctsd−/−) receive AAV9-mediated CTSD gene delivery via intracerebroventricular injection (1×10^10 vg, single dose), THEN brain tissue harvested at 4 weeks post-injection will sho | Restoration of brain lysosomal protease activity to ≥30% of heterozygous control levels and ≥25% reduction in cortical autofluorescence at 4 weeks | — no observation — | pending | 0.00 |