MAP6 stability activity may suppress adjacent tau lability activity through direct physical interaction or by altering tubulin post-translational modifications
Prediction: MAP6 overexpression will extend stability into adjacent tau-rich regions; MAP6 knockout will extend lability into MAP6-rich regions
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Curated Mechanism Pathway
Curated pathway diagram from expert analysis
flowchart TD
A["MAP6 Occupancy on Microtubules Cold-Stable Cytoskeletal Support"]
B["Tau/MAPT Lattice Competition Dynamic Binding Balance"]
C["Synaptic Remodeling Signals NMDA-Linked Cytoskeletal Plasticity"]
D["Axonal Transport and Branching Circuit Adaptation"]
E["MAP6-Tau Imbalance Rigid or Unstable Cytoskeleton"]
A --> B
B --> C
C --> D
E -.->|"disrupts"| B
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style D fill:#1b5e20,stroke:#81c784,color:#81c784
style E fill:#b71c1c,stroke:#ef9a9a,color:#ef9a9a
Median TPM across 13 brain regions for MAP6 from GTEx v10.
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8 citations7 with PMID7 mediumValidation: 0%6 supporting / 2 opposing
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Evidence Matrix — sortable by strength/year, click Abstract to expand
Evidence Types
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MECH 3CLIN 1GENE 4EPID 0
Claim
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PMIDs
Abstract
Tau and MAP6 establish labile and stable domains o…
MAP6 stability activity may suppress adjacent tau …
Supporting
MECH
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Legacy Card View — expandable citation cards
✓ Supporting Evidence
6
MAP6 stability activity may suppress adjacent tau lability activity through direct physical interaction or by …▼
MAP6 stability activity may suppress adjacent tau lability activity through direct physical interaction or by altering tubulin post-translational modifications
Tau and MAP6 establish labile and stable domains on microtubules.MEDIUM
Tau/MAP6 antagonism is shown in neuronal development models, but this does not establish that the same balance…MEDIUM▼
Tau/MAP6 antagonism is shown in neuronal development models, but this does not establish that the same balance drives adult neurodegeneration progression or treatment response.
A microtubule-stabilizing peptide strategy failed to show clinical benefit in progressive supranuclear palsy, …MEDIUM▼
A microtubule-stabilizing peptide strategy failed to show clinical benefit in progressive supranuclear palsy, cautioning against simple cytoskeletal-stabilization translation in tauopathy.
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IF MAP6 is overexpressed 2-fold in primary mouse cortical neurons via AAV2/9 transduction, THEN the ratio of pS396-tau to total tau in detergent-soluble fractions will decrease by at least 30% compared to control-transduced neurons within 7 days post-transduction
pendingconf: 0.45
Expected outcome: Decreased tau phosphorylation at Ser396 by ≥30% in MAP6-overexpressing neurons as measured by quantitative western blot (normalized to β3-tubulin loading control)
Falsified by: No significant change (<15%) in pS396-tau/total tau ratio between MAP6-overexpression and control conditions, or increased rather than decreased phosphorylation
Method: Primary cultures of E18 mouse cortical neurons transduced with AAV2/9-CAG-MAP6 or AAV2/9-CAG-eGFP (MOI 5×10^5), harvested at DIV14 for biochemical fractionation and quantitative immunoblot analysis
IF MAP6 is genetically ablated in iPSC-derived cortical neurons using CRISPR/Cas9, THEN the proportion of neurons exhibiting cytosolic mislocalization of tau (co-localization ratio <0.3 with axonal marker Tau1) will increase by at least 2-fold compared to isogenic control lines within 21 days of differentiation
pendingconf: 0.38
Expected outcome: At least 40% of MAP6-knockout neurons showing tau mislocalization vs. <20% in controls, quantified by high-content immunofluorescence imaging and automated neurite tracing
Falsified by: No difference (<1.3-fold) in tau mislocalization between MAP6-KO and control lines, or tau correctly localized in >70% of MAP6-KO neurons
Method: iPSC lines (2 independent clones per genotype, n=3 lines total) from healthy donor differentiated to cortical neurons for 28 days; MAP6 knockout confirmed by sequencing and western blot; Tau-1 and MAP2 immunostaining analyzed by IN Carta or similar high-content platform
Knowledge Subgraph (0 edges)
No knowledge graph edges recorded
Predicted Protein Structure
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MAP6 — AlphaFold Prediction Q96JE9Click to expand 3D viewer
AI-predicted structure from AlphaFold | Powered by Mol* | Rotate: click+drag | Zoom: scroll | Reset: right-click