Nanobodies that recognize specific tau conformational epitopes and simultaneously possess membrane-disrupting activity could achieve selective penetration by binding surface-exposed pathological tau and then disrupting the associated membrane locally.
Auto-built from this analysis's top knowledge-graph edges.
graph TD
phosphatidylserine_exposu["phosphatidylserine exposure"] -->|associated with| APOPTOSIS["APOPTOSIS"]
pH_sensitive_membrane_fus["pH-sensitive_membrane_fusion_domain"] -->|activates| acidic_microenvironment["acidic_microenvironment"]
phosphatidylserine_bindin["phosphatidylserine-binding_domain"] -->|binds| phosphatidylserine["phosphatidylserine"]
curvature_sensitive_cell_["curvature-sensitive_cell_penetrating_peptide"] -->|penetrates| curved_membranes["curved_membranes"]
ATP_depleted_environment["ATP-depleted_environment"] -->|enables| membrane_penetration["membrane_penetration"]
tau_protein["tau_protein"] -->|interacts with| phosphatidylserine_1["phosphatidylserine"]
tau_protein_2["tau_protein"] -->|induces| membrane_curvature["membrane_curvature"]
tau_aggregation["tau_aggregation"] -->|causes| pH_acidification["pH_acidification"]
tau_aggregation_3["tau_aggregation"] -->|disrupts| cholesterol_depletion["cholesterol_depletion"]
tau_conformational_change["tau_conformational_change"] -->|triggers| membrane_disruption["membrane_disruption"]
tau_aggregation_4["tau_aggregation"] -->|causes| ATP_depletion["ATP_depletion"]
tau_aggregation_5["tau_aggregation"] -->|disrupts| membrane_asymmetry["membrane_asymmetry"]
style phosphatidylserine_exposu fill:#4fc3f7,stroke:#333,color:#000
style APOPTOSIS fill:#ce93d8,stroke:#333,color:#000
style pH_sensitive_membrane_fus fill:#4fc3f7,stroke:#333,color:#000
style acidic_microenvironment fill:#4fc3f7,stroke:#333,color:#000
style phosphatidylserine_bindin fill:#4fc3f7,stroke:#333,color:#000
style phosphatidylserine fill:#4fc3f7,stroke:#333,color:#000
style curvature_sensitive_cell_ fill:#4fc3f7,stroke:#333,color:#000
style curved_membranes fill:#4fc3f7,stroke:#333,color:#000
style ATP_depleted_environment fill:#4fc3f7,stroke:#333,color:#000
style membrane_penetration fill:#4fc3f7,stroke:#333,color:#000
style tau_protein fill:#4fc3f7,stroke:#333,color:#000
style phosphatidylserine_1 fill:#4fc3f7,stroke:#333,color:#000
style tau_protein_2 fill:#4fc3f7,stroke:#333,color:#000
style membrane_curvature fill:#4fc3f7,stroke:#333,color:#000
style tau_aggregation fill:#4fc3f7,stroke:#333,color:#000
style pH_acidification fill:#4fc3f7,stroke:#333,color:#000
style tau_aggregation_3 fill:#4fc3f7,stroke:#333,color:#000
style cholesterol_depletion fill:#4fc3f7,stroke:#333,color:#000
style tau_conformational_change fill:#4fc3f7,stroke:#333,color:#000
style membrane_disruption fill:#4fc3f7,stroke:#333,color:#000
style tau_aggregation_4 fill:#4fc3f7,stroke:#333,color:#000
style ATP_depletion fill:#4fc3f7,stroke:#333,color:#000
style tau_aggregation_5 fill:#4fc3f7,stroke:#333,color:#000
style membrane_asymmetry fill:#4fc3f7,stroke:#333,color:#000No linked papers recorded for this hypothesis yet.
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 MAPT.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF the anti‑tau conformational nanobody (Nb‑TauM) is applied at 100 nM to supported lipid bilayers pre‑coated with pathological tau (P301S) THEN a measurable increase in membrane permeability will be | ≥20 % calcein release from tau‑coated supported lipid bilayers after 30 min exposure to Nb‑TauM. | — no observation — | pending | 0.60 |
| IF HEK293T cells expressing surface‑exposed 2N4R P301S tau are treated with 100 nM Nb‑TauM for 2 h THEN the proportion of Yo‑Pro‑1‑positive cells will increase by ≥2‑fold compared with wild‑type tau‑e | ≥2‑fold increase in Yo‑Pro‑1 uptake (≥15 % Yo‑Pro‑1‑positive cells) in P301S‑tau‑expressing HEK293T cells after 2 h of Nb‑TauM treatment. | — no observation — | pending | 0.55 |