TET Enzyme Enhancement to Prevent Aberrant DNA Methylation
Curated pathway from expert analysis
flowchart TD
A["TET1/TET2/TET3<br/>DNA Demethylase丰度"]
B["5mC to 5hmC<br/>Conversion Active"]
C["Aberrant DNA Methylation<br/>Prevention and Reversal"]
D["Neuronal Identity Genes<br/>Expression Restored"]
E["Epigenetic Age<br/>Rejuvenation"]
F["Neurodegeneration<br/>Progression Slowed"]
G["TET Enhancement<br/>as Epigenetic Therapy"]
A --> B
B --> C
C --> D
D --> E
E --> F
G -.->|"promotes"| A
style A fill:#1a237e,stroke:#4fc3f7,color:#4fc3f7
style F fill:#1b5e20,stroke:#a5d6a7,color:#a5d6a7No linked papers recorded for this hypothesis yet.
No curated PDB or AlphaFold mapping for TET1 yet. Search RCSB →
Median TPM across 13 brain regions for TET1/TET2/TET3 enzymes 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 TET1.
Run python3 scripts/backfill_hypothesis_depmap.py to populate.
| Prediction | Predicted | Observed | Status | Conf |
|---|---|---|---|---|
| IF amyloid-positive older adults (age 65-85) are stratified into high vs. low peripheral blood mononuclear cell TET2 activity quartiles and followed longitudinally, THEN the low TET2 activity quartile | Faster cognitive decline measured by ADAS-Cog12 score trajectory; higher rate of conversion from MCI to probable AD dementia | — no observation — | pending | 0.55 |
| IF TET2 expression is genetically enhanced via CRISPR activation in human iPSC-derived cortical neurons exposed to oxidative stress (modeling neurodegeneration), THEN 5-hydroxymethylcytosine (5hmC) le | Increased 5hmC/5mC ratio at target gene promoters; reduced DNA methylation burden at neuroprotective genes | — no observation — | pending | 0.65 |