| #1 |
Chaperone-Mediated APOE4 Refolding Enhancement |
HSPA1A, HSP90AA1, DNAJB1, FKBP5 |
0.607 |
$0.61 |
| Upregulating specific molecular chaperones (HSP70, HSP90) or co-chaperones could enhance proper APOE4 folding and prevent domain interaction. This approach would leverage endogenous quality control me... |
| #2 |
Targeted APOE4-to-APOE3 Base Editing Therapy |
APOE |
0.583 |
$0.58 |
| CRISPR-based cytosine base editors could precisely convert the C334T mutation back to wild-type, effectively transforming APOE4 carriers into APOE3 genotype. This would eliminate the root cause of dom... |
| #3 |
APOE4 Allosteric Rescue via Small Molecule Chaperones |
APOE |
0.575 |
$0.57 |
| Small molecules targeting the hinge region between APOE4 domains could stabilize the native APOE3-like conformation, preventing pathological domain interaction. These allosteric modulators would resto... |
| #4 |
Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs) |
APOE |
0.528 |
$0.53 |
| Engineered PROTACs could selectively recruit APOE4 (but not APOE3) to E3 ligases for ubiquitin-mediated degradation, based on the unique structural features of domain-interacted APOE4. This would redu... |
| #5 |
Competitive APOE4 Domain Stabilization Peptides |
APOE |
0.481 |
$0.48 |
| Cell-penetrating peptides designed to mimic the N-terminal domain could competitively bind to the C-terminal domain of APOE4, preventing pathological self-interaction. These peptides would act as mole... |
| #6 |
Interfacial Lipid Mimetics to Disrupt Domain Interaction |
APOE |
0.437 |
$0.44 |
| Synthetic lipid-like molecules could competitively bind to the aberrant interdomain interface of APOE4, forcing domains apart and restoring normal lipid binding conformation. These molecules would mim... |
| #7 |
Pharmacological Enhancement of APOE4 Glycosylation |
ST6GAL1, FUT8 |
0.432 |
$0.43 |
| Modulating glycosyltransferases could add stabilizing glycan modifications to APOE4, preventing domain interaction through steric hindrance. Enhanced sialylation or fucosylation could specifically tar... |