| #1 |
LRP1-Dependent Tau Uptake Disruption |
LRP1 |
0.725 |
$0.72 |
| Deploy selective small molecule inhibitors targeting the tau-binding domain of LRP1 to prevent cellular uptake of pathological tau species. This would block the master regulatory mechanism controlling... |
| #2 |
TREM2-mediated microglial tau clearance enhancement |
TREM2 |
0.665 |
$0.67 |
| Activate TREM2 signaling pathways to reprogram microglia from tau-propagating phenotype to tau-clearing phenotype. This would convert microglia from facilitators of tau spread into therapeutic allies ... |
| #3 |
Extracellular Vesicle Biogenesis Modulation |
CHMP4B |
0.570 |
$0.57 |
| Target ESCRT-III complex components (CHMP4B, VPS4) to selectively reduce tau-containing extracellular vesicle formation without completely blocking EV biogenesis. This would preserve beneficial cell-t... |
| #4 |
VCP-Mediated Autophagy Enhancement |
VCP |
0.525 |
$0.53 |
| Design selective allosteric activators of VCP/p97 ATPase activity specifically for tau-containing autophagosome processing. This would enhance the cellular clearance of tau aggregates before they can ... |
| #5 |
HSP90-Tau Disaggregation Complex Enhancement |
HSP90AA1 |
0.460 |
$0.46 |
| Design allosteric modulators that specifically enhance HSP90's tau disaggregation activity without affecting its other client proteins. These compounds would promote the dissolution of tau seeds befor... |
| #6 |
Synaptic Vesicle Tau Capture Inhibition |
SNAP25 |
0.375 |
$0.38 |
| Target SNAP25 interactions to prevent tau uptake at presynaptic terminals during vesicle recycling. Modified SNAP25 peptides could competitively inhibit pathological tau binding to synaptic vesicle ma... |
| #7 |
Trans-Synaptic Adhesion Molecule Modulation |
NLGN1 |
0.330 |
$0.33 |
| Develop selective modulators of neurexin-neuroligin interactions to create 'synaptic barriers' that prevent tau transfer between connected neurons while preserving synaptic transmission. This would co... |