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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 →
2AMPK hypersensitivity in astrocytes creates enhanced mitochondrial rescue respo…
neurodegeneration therapeutic 31 ev
h-43f72e21
PRKAA1validated0.8332026-05-16Open →
3SASP-Mediated Complement Cascade Amplification
neurodegeneration mechanistic 30 ev
h-58e4635a
C1Q/C3validated0.8222026-05-16Open →
4Selective APOE4 Degradation via Proteolysis Targeting Chimeras (PROTACs)
neurodegeneration mechanistic 77 ev
h-11795af0
APOEpromoted0.7952026-05-13Open →
5Senescent Microglia Resolution via Maresins-Senolytics Combination
neurodegeneration therapeutic 27 ev
h-3f02f222
BCL2L1debated0.7912026-05-16Open →
6Competitive APOE4 Domain Stabilization Peptides
neurodegeneration mechanistic 73 ev
h-d0a564e8
APOEpromoted0.7842026-05-13Open →
7SASP-Driven Aquaporin-4 Dysregulation
neurodegeneration mechanistic 30 ev
h-807d7a82
AQP4promoted0.7822026-05-13Open →
8Transcriptional Autophagy-Lysosome Coupling
neurodegeneration mechanistic 50 ev
h-ae1b2beb
FOXO1promoted0.7772026-05-16Open →
9Dual-Domain Antibodies with Engineered Fc-FcRn Affinity Modulation
neurodegeneration therapeutic 35 ev
h-23a3cc07
FCGRTpromoted0.7732026-05-16Open →
10APOE4 Allosteric Rescue via Small Molecule Chaperones
neurodegeneration mechanistic 55 ev
h-44195347
APOEdebated0.7652026-05-13Open →
11SASP-Mediated Cholinergic Synapse Disruption
neurodegeneration mechanistic 32 ev
h-1acdd55e
MMP2/MMP9promoted0.7632026-05-13Open →
12Targeted APOE4-to-APOE3 Base Editing Therapy
neurodegeneration therapeutic 54 ev
h-a20e0cbb
APOEdebated0.7582026-05-13Open →
13Multi-Modal Stress Response Harmonization
neurodegeneration mechanistic 17 ev
h-1e564178
NR3C1/CRH/TNFApromoted0.7562026-05-13Open →
14Senescence-Activated NAD+ Depletion Rescue
neurodegeneration therapeutic 23 ev
h-cb833ed8
CD38/NAMPTpromoted0.7552026-05-13Open →
15Circadian-Synchronized Proteostasis Enhancement
neurodegeneration therapeutic 19 ev
h-0e0cc0c1
CLOCK/ULK1promoted0.7442026-05-13Open →
16Smartphone-Detected Motor Variability Correction
neurodegeneration mechanistic 23 ev
h-072b2f5d
DRD2/SNCApromoted0.7422026-05-13Open →
17Senescent Cell Mitochondrial DNA Release
neurodegeneration mechanistic 28 ev
h-1a34778f
CGAS/STING1/DNASE2debated0.7422026-05-16Open →
18Near-infrared light therapy stimulates COX4-dependent mitochondrial motility en…
neurodegeneration therapeutic 35 ev
h-fd1562a3
COX4I1debated0.7422026-05-16Open →
19Epigenetic Memory Erasure via TET2 Activation
neurodegeneration mechanistic 31 ev
h-d2722680
TET2debated0.7412026-05-16Open →
20PARP1 Inhibition Therapy
neurodegeneration therapeutic 45 ev
h-69919c49
PARP1promoted0.7382026-05-13Open →
21Aquaporin-4 Polarization Rescue
neurodegeneration therapeutic 31 ev
h-c8ccbee8
AQP4debated0.7322026-05-13Open →
22Senescence-Associated Myelin Lipid Remodeling
neurodegeneration mechanistic 31 ev
h-bb518928
PLA2G6/PLA2G4Adebated0.7322026-05-16Open →
23Senescence-Induced Lipid Peroxidation Spreading
neurodegeneration mechanistic 19 ev
h-7957bb2a
GPX4/SLC7A11debated0.7302026-05-13Open →
24Adenosine-Astrocyte Metabolic Reset
neurodegeneration mechanistic 23 ev
h-41bc2d38
ADORA2Apromoted0.7302026-05-16Open →
25Phase-Separated Organelle Targeting
neurodegeneration mechanistic 27 ev
h-ec731b7a
G3BP1debated0.7292026-05-13Open →
26Synthetic Biology BBB Endothelial Cell Reprogramming
neurodegeneration therapeutic 14 ev
h-84808267
TFR1, LRP1, CAV1, ABCB1debated0.7272026-05-13Open →
27Metabolic Switch Targeting for A1→A2 Repolarization
neurodegeneration mechanistic 31 ev
h-a1b56d74
HK2debated0.7262026-05-13Open →
28TFAM overexpression creates mitochondrial donor-recipient gradients for directe…
neurodegeneration mechanistic 25 ev
h-98b431ba
TFAMdebated0.7252026-05-13Open →
29Interfacial Lipid Mimetics to Disrupt Domain Interaction
neurodegeneration mechanistic 46 ev
h-99b4e2d2
APOEdebated0.7232026-05-16Open →
30Circadian Rhythm Entrainment of Reactive Astrocytes
neurodegeneration mechanistic 26 ev
h-5706bbd7
BMAL1debated0.7222026-05-13Open →
31Sleep Spindle-Synaptic Plasticity Enhancement
neurodegeneration therapeutic 27 ev
h-8d270062
CACNA1Gdebated0.7212026-05-13Open →
32Stress Granule Phase Separation Modulators
neurodegeneration mechanistic 23 ev
h-97aa8486
G3BP1debated0.7202026-05-13Open →
33Magnetosonic-Triggered Transferrin Receptor Clustering
neurodegeneration mechanistic 25 ev
h-aa2d317c
TFR1debated0.7192026-05-13Open →
34Retinal Vascular Microcirculation Rescue
neurodegeneration therapeutic 18 ev
h-35f04e1b
PDGFRB/ANGPT1debated0.7182026-05-13Open →
35Engineered Apolipoprotein E4-Neutralizing Shuttle Peptides
neurodegeneration mechanistic 27 ev
h-b948c32c
APOE, LRP1, LDLRdebated0.7182026-05-16Open →
36Circadian-Synchronized LRP1 Pathway Activation
neurodegeneration mechanistic 18 ev
h-7e0b5ade
LRP1, MTNR1A, MTNR1Bdebated0.7142026-05-13Open →
37Purinergic Signaling Polarization Control
neurodegeneration mechanistic 16 ev
h-0758b337
P2RY1 and P2RX7debated0.7132026-05-13Open →
38Noradrenergic-Tau Propagation Blockade
neurodegeneration therapeutic 14 ev
h-4113b0e8
ADRA2Adebated0.7112026-05-13Open →
39HDAC3-Selective Inhibition for Clock Reset
neurodegeneration therapeutic 19 ev
h-a9571dbb
HDAC3debated0.7102026-05-16Open →
40Metabolic Circuit Breaker via Lipid Droplet Modulation
neurodegeneration mechanistic 22 ev
h-3d993b5d
PLIN2debated0.7092026-05-13Open →
41Autophagosome Maturation Checkpoint Control
neurodegeneration mechanistic 17 ev
h-5e68b4ad
STX17debated0.7092026-05-13Open →
42Matrix Stiffness Normalization via Targeted Lysyl Oxidase Inhibition
neurodegeneration therapeutic 17 ev
h-82922df8
LOX/LOXL1-4debated0.7092026-05-13Open →
43Orexin-Microglia Modulation Therapy
neurodegeneration therapeutic 16 ev
h-8597755b
HCRTR2debated0.7072026-05-13Open →
44TET2-Mediated Demethylation Rejuvenation Therapy
neurodegeneration therapeutic 18 ev
h-d7121bcc
TET2debated0.7062026-05-13Open →
45Lysosomal Enzyme Trafficking Correction
neurodegeneration mechanistic 21 ev
h-b3d6ecc2
IGF2Rdebated0.7062026-05-13Open →
46Endothelial Glycocalyx Regeneration via Syndecan-1 Upregulation
neurodegeneration mechanistic 17 ev
h-fb56c8a0
SDC1debated0.7052026-05-13Open →
47Microglial Efferocytosis Enhancement via GPR32 Superagonists
neurodegeneration mechanistic 17 ev
h-470ff83e
CMKLR1debated0.7042026-05-16Open →
48Purinergic P2Y12 Inverse Agonist Therapy
neurodegeneration therapeutic 24 ev
h-f99ce4ca
P2RY12debated0.7032026-05-13Open →
49Microglial Purinergic Reprogramming
neurodegeneration mechanistic 20 ev
h-5daecb6e
P2RY12debated0.7012026-05-16Open →
50Mechanosensitive Ion Channel Reprogramming
neurodegeneration mechanistic 23 ev
h-db6aa4b1
PIEZO1 and KCNK2debated0.7002026-05-13Open →
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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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