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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.

88
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#HypothesisTarget geneStatusCompositeUpdated
1p38α Inhibitor and PRMT1 Activator Combination to Restore Physiological TDP-43…
neurodegeneration combination 16 ev
h-ccc05373
MAPK14/PRMT1validated0.8952026-05-16Open →
2HSPB1 Phosphorylation Mimetics to Promote Protective TDP-43 Liquid-Liquid Phase…
neurodegeneration combination 19 ev
h-ff0d545d
HSPB1validated0.8202026-05-14Open →
3CLU/APOE Duality in Amyloid Clearance Determines Cell-Type-Specific Vulnerabili…
neurodegeneration combination 20 ev
h-0bcda2e0
APOE, CLUvalidated0.8112026-05-13Open →
4Integrated Biomarker Panel for Therapeutic Window Identification
neurodegeneration combination 21 ev
h-ecd9ed6c
CHI3L1promoted0.7842026-05-13Open →
5TREM2-mediated microglial tau clearance enhancement
neurodegeneration combination 15 ev
SDA-2026-04-02-gap-tau-prop-20260402003221-H002
TREM2proposed0.7802026-05-16Open →
6TREM2 Agonism to Restore Microglial Phagocytosis Across Both Pathologies
neurodegeneration combination 9 ev
h-15a8468c
TREM2, TYROBP (DAP12), PLCG2, SYKpromoted0.7352026-05-16Open →
7Microglial TREM2-Complement Axis Modulation
neurodegeneration combination 20 ev
h-3616325a
TREM2 and C3promoted0.7262026-05-13Open →
8ASO-Mediated Exon Skipping to Restore FUS-TAZ Chaperone Axis
neurodegeneration combination 13 ev
h-6756097b
FUSpromoted0.7202026-05-16Open →
9Early Proteasome Restoration Therapy
neurodegeneration combination 14 ev
h-9588dd18
PSMCpromoted0.7122026-05-13Open →
10Ferroptosis Inhibition for α-Synuclein Neuroprotection
neurodegeneration combination 36 ev
h-2c776894
GPX4promoted0.7052026-05-13Open →
11H2: Indole-3-Propionate (IPA) as the Actual Neuroprotective Effector
neurodegeneration combination 13 ev
h-66078909
PXR (NR1I2), IDO1promoted0.6992026-05-13Open →
12TFEB-Independent Autophagy Bypass
neurodegeneration combination 16 ev
h-1e4bba56
ULK1promoted0.6972026-05-13Open →
13cGAS-STING Senescence Circuit Disruption
neurodegeneration combination 20 ev
h-bbe4540f
CGAS, STING1promoted0.6912026-05-13Open →
14Multi-Target Synergy via Presynaptic Vesicle Hub Convergence
neurodegeneration combination 11 ev
h-2651ca91
TH, VMAT2, DAT, GCH1, BDNF, SNCA (presynaptic hub)proposed0.6832026-05-14Open →
15Astrocyte-Selective APOE4 Silencing via Lipid Nanoparticles
neurodegeneration combination 31 ev
h-541d61c3
APOE4promoted0.6822026-05-13Open →
16HDAC6 Activation as SCFA-Mediated Neuroprotective Mechanism
neurodegeneration combination 12 ev
h-ca454967
HDAC6, HSP90AA1proposed0.6822026-05-14Open →
17CRISPR-Mediated Mitochondrial Genome Editing for Complex I Dysfunction
neurodegeneration combination 11 ev
h-420db533
MT-ND1, MT-ND4, MT-ND6proposed0.6812026-05-13Open →
18Cell-Type Specific TFEB Modulation
neurodegeneration combination 20 ev
h-b9acf0c9
TFEBpromoted0.6772026-05-13Open →
19White Matter Oligodendrocyte Protection via CXCL10 Inhibition
neurodegeneration combination 17 ev
h-724e3929
CXCL10promoted0.6752026-05-13Open →
20Dissociating SCFA's Dual Signaling Through GPR43/GPR41 Biased Agonism
neurodegeneration combination 12 ev
h-ded1734f
FFAR2, FFAR3, NLRP3promoted0.6702026-05-14Open →
21White Matter Vulnerability Prevention via Oligodendrocyte Protection
neurodegeneration combination 17 ev
h-c5698ce3
CXCL10promoted0.6672026-05-13Open →
22Oligodendrocyte DNA Repair Enhancement Therapy
neurodegeneration combination 11 ev
h-fa7ac9cb
PARP1 and XRCC1proposed0.6652026-05-13Open →
23PARP1 Inhibition Blocks Poly(PR)-Triggered DNA Damage and Subsequent p53 Activa…
neurodegeneration combination 9 ev
h-737c3be8
PARP1promoted0.6612026-05-13Open →
24Complement C1QA Inhibition Synergizes with PV Interneuron Modulation
neurodegeneration combination 10 ev
h-329b1a79
C1QA, PVALBproposed0.6592026-05-14Open →
25TREM2 Activation as an Amplification Node for R136S Protection
neurodegeneration combination 12 ev
h-69c9d059
TREM2proposed0.6572026-05-14Open →
26Parvalbumin Interneuron Vulnerability Links Lactate Transport to Gamma Oscillat…
neurodegeneration combination 13 ev
h-7c93c300
PVALB, SLC16A1/MCT1promoted0.6562026-05-16Open →
27Astrocyte-Microglia Communication Rebalancing via Cytokine Modulation
neurodegeneration combination 7 ev
h-89500d80
IL1A, TNF, C1Qpromoted0.6552026-05-16Open →
28Microbiota-Microglia Axis Modulation
neurodegeneration combination 43 ev
h-6f21f62a
Multipledebated0.6512026-05-13Open →
29Astrocyte APOE4-Specific Lipid Metabolism Correction
neurodegeneration combination 5 ev
h-3be15ed2
APOEproposed0.6512026-05-16Open →
30Oligodendrocyte Remyelination Enhancement
neurodegeneration combination 21 ev
h-e003a35e
TREM2proposed0.6442026-05-13Open →
31Dual Calpain/Cathepsin B Inhibition as Primary Neuroprotective Strategy
neurodegeneration combination 10 ev
h-699c0d72
—promoted0.6442026-05-16Open →
32Mitochondrial NAD+ Salvage Enhancement
neurodegeneration combination 16 ev
h-3da804f5
STING1proposed0.6392026-05-13Open →
33Acid-Degradable LNP-Mediated Prenatal CRISPR Intervention for Severe Neurodevel…
neurodegeneration combination 6 ev
h-10b5bf6f
SOD1, HTT, TARDBPproposed0.6382026-05-13Open →
34Selective Neuronal Vulnerability Network Targeting
neurodegeneration combination 14 ev
h-0f2b2111
Cell-type specific vulnerability markersproposed0.6382026-05-13Open →
35Astrocyte Metabolic Reprogramming via APOE4 Correction
neurodegeneration combination 26 ev
h-d8f2bbc9
APOEpromoted0.6362026-05-13Open →
36TREM2-Dependent Microglial Phagocytosis Acts as a Strain Selection Filter
neurodegeneration combination 10 ev
h-dca86efa
TREM2proposed0.6362026-05-13Open →
37DLK MAPK Pathway Inhibition to Block Tau-Induced Neurotoxicity Without Directly…
neurodegeneration combination 11 ev
h-917f37cf
MAP2K7/MAP3K12promoted0.6342026-05-13Open →
38Disease-Associated Microglia Metabolic Reprogramming
neurodegeneration combination 15 ev
h-2531ed61
TREM2promoted0.6312026-05-16Open →
39Selective Cholinergic Protection via APP Pathway Modulation
neurodegeneration combination 30 ev
h-0d576989
APPproposed0.6292026-05-13Open →
40Cardiovascular-Neuroinflammatory Dual Targeting
neurodegeneration combination 9 ev
h-6f1e8d32
TNF/IL6debated0.6272026-05-16Open →
41Myelin Sulfatide Restoration
neurodegeneration combination 10 ev
h-d9604ebf
GAL3ST1promoted0.6232026-05-16Open →
42Microglial ACE Enhancement for Amyloid Clearance
neurodegeneration combination 27 ev
h-1e28311b
ACEproposed0.6222026-05-13Open →
43H7: Enteric Nervous System Alpha-Synuclein Propagation Blocker via Gut Barrier…
neurodegeneration combination 15 ev
h-a5186bb8
IL-22, REG3G, zonulinpromoted0.6202026-05-13Open →
44Cross-Cell Type Synaptic Rescue via Tripartite Synapse Restoration
neurodegeneration combination 5 ev
h-019c56c1
SYN1, SLC1A2, and CX3CR1proposed0.6202026-05-13Open →
45CSF Biomarker-Guided ABCA7 Therapeutic Dosing
neurodegeneration combination 9 ev
h-bc635955
ABCA7 with biomarker-guided dosingpromoted0.6192026-05-14Open →
46Lysosomal pH Restoration Upstream of TFEB
neurodegeneration combination 7 ev
h-6b394be1
ATP6V1Aproposed0.6192026-05-13Open →
47BH4 Cofactor Restoration as Primary Driver of >500-Fold Dopamine Elevation
neurodegeneration combination 12 ev
h-a01166ee
GCH1, TH, BH4 pathwayproposed0.6182026-05-14Open →
48Perinatal Immune Challenge Prevention
neurodegeneration combination 42 ev
h-8f9633d9
Multipledebated0.6162026-05-16Open →
49APOE4-Lipid Metabolism Correction
neurodegeneration combination 28 ev
h-69bde12f
APOEdebated0.6102026-05-16Open →
50Temporal TFEB Modulation Therapy
neurodegeneration combination 18 ev
h-1775578a
TFEBproposed0.6092026-05-16Open →
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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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