| #1 |
Microglial Purinergic Reprogramming |
P2RY12 |
0.606 |
$0.61 |
| P2Y12 receptor expression levels determine whether microglia promote tufted astrocyte formation (low P2Y12) versus astrocytic plaques (high P2Y12) by controlling ATP-mediated tau propagation signals. ... |
| #2 |
Aquaporin-4 Polarization Rescue |
AQP4 |
0.589 |
$0.59 |
| 4R-tau strains disrupt AQP4 polarization differently in brainstem vs cortical astrocytes, creating distinct perivascular clearance failures. Restoring AQP4 polarity through α-syntrophin modulation cou... |
| #3 |
Sphingolipid Metabolism Reprogramming |
CERS2 |
0.551 |
$0.55 |
| Regional differences in ceramide synthase isoform expression (CERS2 vs CERS6) create distinct membrane environments that favor specific 4R-tau conformational states. Pharmacological CERS modulation co... |
| #4 |
Complement C1q Subtype Switching |
C1QA |
0.513 |
$0.51 |
| Brainstem astrocytes express C1qA-dominant complexes promoting tufted morphology, while cortical astrocytes express C1qC-dominant complexes favoring plaque formation. C1q subunit-selective inhibitors ... |
| #5 |
Glial Glycocalyx Remodeling Therapy |
HSPG2 |
0.505 |
$0.51 |
| PSP and CBD tau strains differentially interact with region-specific glial glycocalyx compositions, determining astrocytic morphology. Enzymatic remodeling of heparan sulfate proteoglycans could redir... |
| #6 |
Ephrin-B2/EphB4 Axis Manipulation |
EPHB4 |
0.485 |
$0.48 |
| Astrocytic ephrin-B2 expression creates regional 'tau reception zones' that determine whether incoming 4R-tau forms tufts or plaques. EphB4 activation therapy could reprogram astrocytes to resist path... |
| #7 |
Netrin-1 Gradient Restoration |
NTN1 |
0.353 |
$0.35 |
| Loss of developmental netrin-1 gradients in adult brain allows inappropriate 4R-tau strain migration between regions. Therapeutic netrin-1 delivery could re-establish compartmentalization barriers, pr... |