Aberrant MAP6 function may contribute to tau-independent cytoskeletal defects in neurodegeneration, and stabilizing MAP6-microtubule interactions pharmacologically could compensate for Tau pathology
Prediction: Small molecules enhancing MAP6-microtubule binding will ameliorate cytoskeletal defects in tau knockout neurons and improve neuronal survival in amyloid toxicity models
Curated pathway from expert analysis
flowchart TD
A["MAPT/Tau Occupancy<br/>Dynamic Microtubule Binding"]
B["MAP6 Occupancy<br/>Cold-Stable Domain Support"]
C["Shared Microtubule Lattice<br/>Domain Allocation Competition"]
D["GSK3B/CRMP2 Cue Integration<br/>Plasticity Signaling"]
E["Axonal Remodeling Balance<br/>Stable vs Labile Segments"]
F["Transport and Branching<br/>Adaptive Circuit Plasticity"]
G["Tau-MAP6 Imbalance<br/>Rigid or Unstable Cytoskeleton"]
A --> C
B --> C
C --> D
D --> E
E --> F
G -.->|"disrupts"| C
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style B fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#1b5e20,stroke:#81c784,color:#81c784
style G fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9aNo linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for MAP6 yet. Search RCSB →
Median TPM across 13 brain regions for MAP6 from GTEx v10.
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 MAP6.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
No resource usage or linked notebooks recorded for this hypothesis yet.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF 5xFAD amyloid transgenic mice (8 months old) are administered a MAP6 stabilizer (intraperitoneal injection at 20 mg/kg daily for 8 weeks), THEN spatial memory performance on the Morris water maze w | Morris water maze escape latency: ≥25% reduction; Cortical neuron count (NeuN+ cells): ≥20% increase; Insoluble amyloid load: ≤10% change (to confirm direct cyt | — no observation — | pending | 0.55 |
| IF primary cortical neurons from tau knockout mice are treated with a small molecule that enhances MAP6-microtubule binding (e.g., MS-12 or similar compound at 10 μM for 7 days), THEN acetylated α-tub | Acetylated α-tubulin levels: ≥40% increase; Cell viability (MTS assay): ≥30% improvement; Microtubule polymerization rate: ≥25% increase | — no observation — | pending | 0.65 |