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Hypotheses

Top-ranked hypotheses by composite score. Filter by lifecycle status, disease, or target gene; sort by score or recency. Click a row to open evidence, scoring detail, and any live prediction markets referencing it.

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#HypothesisTarget geneStatusCompositeUpdated
1Circadian Glymphatic Entrainment via Targeted Orexin Receptor Modulation
neurodegeneration therapeutic 29 ev
h-9e9fee95
HCRTR1/HCRTR2validated0.8822026-05-13Open →
2SASP-Mediated Complement Cascade Amplification
neurodegeneration mechanistic 30 ev
h-58e4635a
C1Q/C3validated0.8222026-05-16Open →
3Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)
neurodegeneration mechanistic 77 ev
h-11795af0
APOEpromoted0.7952026-05-13Open →
4Senescent Microglia Resolution via Maresins-Senolytics Combination
neurodegeneration therapeutic 27 ev
h-3f02f222
BCL2L1debated0.7912026-05-16Open →
5SASP-Driven Aquaporin-4 Dysregulation
neurodegeneration mechanistic 30 ev
h-807d7a82
AQP4promoted0.7822026-05-13Open →
6Transcriptional Autophagy-Lysosome Coupling
neurodegeneration mechanistic 50 ev
h-ae1b2beb
FOXO1promoted0.7772026-05-16Open →
7Dual-Domain Antibodies with Engineered Fc-FcRn Affinity Modulation
neurodegeneration therapeutic 35 ev
h-23a3cc07
FCGRTpromoted0.7732026-05-16Open →
8APOE4 Allosteric Rescue via Small Molecule Chaperones
neurodegeneration mechanistic 55 ev
h-44195347
APOEdebated0.7652026-05-13Open →
9SASP-Mediated Cholinergic Synapse Disruption
neurodegeneration mechanistic 32 ev
h-1acdd55e
MMP2/MMP9promoted0.7632026-05-13Open →
10Targeted APOE4-to-APOE3 Base Editing Therapy
neurodegeneration therapeutic 54 ev
h-a20e0cbb
APOEdebated0.7582026-05-13Open →
11Multi-Modal Stress Response Harmonization
neurodegeneration mechanistic 17 ev
h-1e564178
NR3C1/CRH/TNFApromoted0.7562026-05-13Open →
12Circadian-Synchronized Proteostasis Enhancement
neurodegeneration therapeutic 19 ev
h-0e0cc0c1
CLOCK/ULK1promoted0.7442026-05-13Open →
13Smartphone-Detected Motor Variability Correction
neurodegeneration mechanistic 23 ev
h-072b2f5d
DRD2/SNCApromoted0.7422026-05-13Open →
14Senescent Cell Mitochondrial DNA Release
neurodegeneration mechanistic 28 ev
h-1a34778f
CGAS/STING1/DNASE2debated0.7422026-05-16Open →
15PARP1 Inhibition Therapy
neurodegeneration therapeutic 45 ev
h-69919c49
PARP1promoted0.7382026-05-13Open →
16Senescence-Associated Myelin Lipid Remodeling
neurodegeneration mechanistic 31 ev
h-bb518928
PLA2G6/PLA2G4Adebated0.7322026-05-16Open →
17Senescence-Induced Lipid Peroxidation Spreading
neurodegeneration mechanistic 19 ev
h-7957bb2a
GPX4/SLC7A11debated0.7302026-05-13Open →
18Synthetic Biology BBB Endothelial Cell Reprogramming
neurodegeneration therapeutic 14 ev
h-84808267
TFR1, LRP1, CAV1, ABCB1debated0.7272026-05-13Open →
19Metabolic Switch Targeting for A1→A2 Repolarization
neurodegeneration mechanistic 31 ev
h-a1b56d74
HK2debated0.7262026-05-13Open →
20Interfacial Lipid Mimetics to Disrupt Domain Interaction
neurodegeneration mechanistic 46 ev
h-99b4e2d2
APOEdebated0.7232026-05-16Open →
21Circadian Rhythm Entrainment of Reactive Astrocytes
neurodegeneration mechanistic 26 ev
h-5706bbd7
BMAL1debated0.7222026-05-13Open →
22Stress Granule Phase Separation Modulators
neurodegeneration mechanistic 23 ev
h-97aa8486
G3BP1debated0.7202026-05-13Open →
23Magnetosonic-Triggered Transferrin Receptor Clustering
neurodegeneration mechanistic 25 ev
h-aa2d317c
TFR1debated0.7192026-05-13Open →
24Retinal Vascular Microcirculation Rescue
neurodegeneration therapeutic 18 ev
h-35f04e1b
PDGFRB/ANGPT1debated0.7182026-05-13Open →
25Engineered Apolipoprotein E4-Neutralizing Shuttle Peptides
neurodegeneration mechanistic 27 ev
h-b948c32c
APOE, LRP1, LDLRdebated0.7182026-05-16Open →
26Circadian-Synchronized LRP1 Pathway Activation
neurodegeneration mechanistic 18 ev
h-7e0b5ade
LRP1, MTNR1A, MTNR1Bdebated0.7142026-05-13Open →
27Purinergic Signaling Polarization Control
neurodegeneration mechanistic 16 ev
h-0758b337
P2RY1 and P2RX7debated0.7132026-05-13Open →
28Metabolic Circuit Breaker via Lipid Droplet Modulation
neurodegeneration mechanistic 22 ev
h-3d993b5d
PLIN2debated0.7092026-05-13Open →
29Autophagosome Maturation Checkpoint Control
neurodegeneration mechanistic 17 ev
h-5e68b4ad
STX17debated0.7092026-05-13Open →
30Matrix Stiffness Normalization via Targeted Lysyl Oxidase Inhibition
neurodegeneration therapeutic 17 ev
h-82922df8
LOX/LOXL1-4debated0.7092026-05-13Open →
31Lysosomal Enzyme Trafficking Correction
neurodegeneration mechanistic 21 ev
h-b3d6ecc2
IGF2Rdebated0.7062026-05-13Open →
32Microglial Efferocytosis Enhancement via GPR32 Superagonists
neurodegeneration mechanistic 17 ev
h-470ff83e
CMKLR1debated0.7042026-05-16Open →
33Microglial Purinergic Reprogramming
neurodegeneration mechanistic 20 ev
h-5daecb6e
P2RY12debated0.7012026-05-16Open →
34Lysosomal Calcium Channel Modulation Therapy
neurodegeneration therapeutic 17 ev
h-8ef34c4c
MCOLN1debated0.6972026-05-16Open →
35Perforant Path Presynaptic Terminal Protection Strategy
neurodegeneration mechanistic 16 ev
h-76888762
PPARGC1Adebated0.6962026-05-16Open →
36Axonal RNA Transport Reconstitution
neurodegeneration mechanistic 20 ev
h-8196b893
HNRNPA2B1debated0.6952026-05-13Open →
37Mitochondrial Transfer Pathway Enhancement
neurodegeneration mechanistic 22 ev
h-969bd8e0
MIRO1debated0.6952026-05-13Open →
38Complement C1q Mimetic Decoy Therapy
neurodegeneration mechanistic 18 ev
h-1fe4ba9b
C1QAdebated0.6952026-05-13Open →
39Astrocytic Lipoxin A4 Pathway Restoration via ALOX15 Gene Therapy
neurodegeneration therapeutic 21 ev
h-ac55ff26
ALOX15debated0.6952026-05-13Open →
40Ocular Immune Privilege Extension
neurodegeneration mechanistic 16 ev
h-6a065252
FOXP3/TGFB1debated0.6922026-05-13Open →
41Extracellular Matrix Stiffness Modulation
neurodegeneration mechanistic 27 ev
h-725c62e9
PIEZO1debated0.6912026-05-13Open →
42Lysosomal Positioning Dynamics Modulation
neurodegeneration mechanistic 21 ev
h-b295a9dd
LAMP1debated0.6862026-05-13Open →
43TREM2 Conformational Stabilizers for Synaptic Discrimination
neurodegeneration mechanistic 29 ev
h-044ee057
TREM2debated0.6852026-05-13Open →
44Pericyte Contractility Reset via Selective PDGFR-β Agonism
neurodegeneration mechanistic 20 ev
h-73e4340b
PDGFRBdebated0.6842026-05-13Open →
45Chaperone-Mediated APOE4 Refolding Enhancement
neurodegeneration therapeutic 19 ev
h-637a53c9
HSPA1A, HSP90AA1, DNAJB1, FKBP5debated0.6802026-05-13Open →
46Osmotic Gradient Restoration via Selective AQP1 Enhancement in Choroid Plexus
neurodegeneration therapeutic 21 ev
h-0dea0ed5
AQP1debated0.6802026-05-13Open →
47Metabolic Reprogramming via Microglial Glycolysis Inhibition
neurodegeneration therapeutic 27 ev
h-38292315
HK2debated0.6722026-05-13Open →
48Aquaporin-4 Polarization Enhancement via TREK-1 Channel Modulation
neurodegeneration therapeutic 15 ev
h-9eae33ba
KCNK2debated0.6682026-05-13Open →
49Mitochondrial-Lysosomal Contact Site Engineering
neurodegeneration mechanistic 16 ev
h-0791836f
RAB7Adebated0.6682026-05-13Open →
50Lipid Droplet Dynamics as Phenotype Switches
neurodegeneration mechanistic 15 ev
h-7d4a24d3
DGAT1 and SOAT1debated0.6662026-05-13Open →
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Hypothesis index sorted by composite score. Each hypothesis is a scientific claim produced by multi-agent analysis, scored on 10 dimensions. Filter by hypothesis_type, target_gene, disease, or status. Links to /hypotheses/[id] for the full scoring breakdown.

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