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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
1IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia Interface
neuroinflammation mechanistic 13 ev
h-2dbf5f1f
IL6R, IL6validated0.8312026-05-14Open →
2STING Antagonists as ALS Therapeutics: Drug Repurposing
neuroinflammation 13 ev
h-6fe30c39bc
STING (TMEM173)validated0.8212026-05-14Open →
3PDE4 Inhibition as Inflammatory Reset for PD Oligodendrocytes
neuroinflammation mechanistic 13 ev
h-67914e81
PDE4A, PDE4B, PDE4Dpromoted0.7792026-05-14Open →
4TREM2 Crosstalk and Synergistic Activation of Phagocytic Transcriptome
neuroinflammation 6 ev
h-adfcd3f146
TREM2/DAP12 (TYROBP)proposed0.7612026-05-14Open →
5Temporal SPP1 Inhibition During Critical Windows
neuroinflammation combination 10 ev
h-655c7f33
SPP1promoted0.7522026-05-13Open →
6Peripheral Monocyte/Macrophage Infiltration Mimicking Microglial Loss
neuroinflammation 10 ev
h-f9dca82e35
CCR2proposed0.7432026-05-14Open →
7Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determines AQP4 Tolerance…
neuroinflammation mechanistic 12 ev
h-ab41908b
AHR, IL10, TNFRSF13B, TIGIT, FOXP3promoted0.7382026-05-14Open →
8Regional TREM2-Dependent Lipid Metabolism Determines Cortical Vulnerability in…
neuroinflammation 8 ev
h-1eaa052225
TREM2proposed0.7212026-05-14Open →
9TGF-β1–SMAD2/3 Axis as Master Suppressor of Microglial Trained Immunity
neuroinflammation 7 ev
h-fcd38787
TGFBR1/TGFBR2 → SMAD4 → SMAD2/3proposed0.7122026-05-14Open →
10PGE2–EP2–cAMP–PKA Axis Displaces Pathological Microglial Memory Traces
neuroinflammation 10 ev
h-be9bab57
PTGER2 (EP2) → ADCY → cAMP → PRKA (PKA) → SIRT1proposed0.6812026-05-14Open →
11Autophagy-Lysosomal Degradation of IBA1 in Stressed Microglia
neuroinflammation 5 ev
h-d7924e2bc6
LC3/P62/SQSTM1proposed0.6812026-05-14Open →
12NLRP3/Mitophagy Coupling Modulation
neuroinflammation combination 15 ev
h-f10d82a7
NLRP3promoted0.6812026-05-13Open →
13Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through…
neuroinflammation 7 ev
h-20db7feba4
cGAS (CGAS) / STING (TMEM173) / IFNAR1/2proposed0.6612026-05-14Open →
14Astrocyte IL-1β as Paracrine Mediator of Microglial Complement Expression
neuroinflammation 6 ev
h-81349dd293
IL1B; IL1R1; MYD88proposed0.6582026-05-14Open →
15C3aR Blockade Disrupts the Microglial-Astrocyte Feedforward Neurotoxic Loop
neuroinflammation combination 13 ev
h-48b29b62
C3AR1, C3, NFKB1promoted0.6512026-05-14Open →
16IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through…
neuroinflammation combination 10 ev
h-88e23c4a
IL10, CSF1R, CD40promoted0.6482026-05-14Open →
17Epigenetic Silencing of AIF1 Gene Locus by Chronic Inflammation
neuroinflammation 5 ev
h-67d4435cb5
DNMT1/DNMT3Aproposed0.6432026-05-14Open →
18Liver-Derived Inflammatory Suppressors Downregulate Microglial IBA1
neuroinflammation 5 ev
h-246051ec90
STAT3/JAK1proposed0.6332026-05-14Open →
19C1Q-Triggered NLRP3 Inflammasome Assembly in Plaque Macrophages
neuroinflammation 7 ev
h-1ac3dd5b75
C1QA/C1QCproposed0.6312026-05-14Open →
20C1Q-Induced Foam Cell Formation via Scavenger Receptor Upregulation
neuroinflammation 7 ev
h-9318aa358d
C1QA/C1QCproposed0.6202026-05-14Open →
21Metabolic Rewiring via SPP1-Induced HIF1α Glycolytic Shift
neuroinflammation 6 ev
h-a93292f54f
HIF1A (HIF1α), MTOR (mTORC1), EGLN1 (PHD2)proposed0.6202026-05-14Open →
22Age-Accelerated miR-155 Upregulation Primes Nigral Microglia for Parkinson's Di…
neuroinflammation 8 ev
h-42f8fa19eb
miR-155proposed0.6102026-05-14Open →
23Microglial priming is primarily epigenetic, with metabolic changes acting as co…
neuroinflammation 5 ev
h-0b67a9f249
KDM6Bproposed0.6092026-05-14Open →
24STING Antagonism Prevents Acute-to-Chronic Neuroinflammation Transition via Int…
neuroinflammation therapeutic 10 ev
h-ed960965
TMEM173 (STING)promoted0.6012026-05-14Open →
25C1Q-Mediated Defective Efferocytosis Driving Necrotic Core Expansion
neuroinflammation 8 ev
h-84be6621ea
C1QA/C1QCproposed0.6002026-05-14Open →
26TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement Cascade
neuroinflammation 5 ev
h-af85b48c8e
TNF; TNFRSF1A; C1R; C1Sproposed0.6002026-05-14Open →
27APOE4 Induces Region-Specific Microglial Senescence Driving Frontal Cortex Neur…
neuroinflammation 8 ev
h-5f98d0e5d4
APOE4proposed0.6002026-05-14Open →
28Aryl Hydrocarbon Receptor (AhR) Activation by Microbiome Metabolites Promotes A…
neuroinflammation combination 11 ev
h-423b50a1
AHR, CYP1A1, NFKB1, IL6promoted0.5972026-05-14Open →
29Selective C1q-CRP vs. C1q-IgG Axis Inhibition
neuroinflammation 5 ev
h-c8d2ea20
C1QA/C1QB/C1QC, CRP, FCGR1Apromoted0.5972026-05-13Open →
30Astrocyte-Derived EV miR-146a-5p Mimics as Erasers of Trained Microglial NF-κB…
neuroinflammation 6 ev
h-cae1ad2e
miR-146a-5p → IRAK1, TRAF6, NOTCH1, HDAC1proposed0.5882026-05-14Open →
31TREM2 Signaling Bifurcation with Independent TYROBP-Independent Homeostatic Mai…
neuroinflammation therapeutic 7 ev
h-9c857387
TREM2promoted0.5862026-05-14Open →
32Female Microglia Exhibit Reduced P2Y12 Expression Conferring Neuroprotection Th…
neuroinflammation 8 ev
h-d3a2216a86
P2RY12proposed0.5802026-05-14Open →
33Astrocyte cGAS/STING Activation Converts Protective into Destructive Neuroinfla…
neuroinflammation 7 ev
h-9f504f5d4d
STING (TMEM173) in astrocytes (GFAP+ cells)proposed0.5802026-05-14Open →
34αvβ3 Integrin-FAK-SYK-CARD9/NF-κB Pathway
neuroinflammation 6 ev
h-6358a464ac
ITGAV/ITGB3 (αvβ3 heterodimer), PTK2 (FAK), SYK, CARD9proposed0.5802026-05-14Open →
35Microglial Priming via NF-κB-Dependent DAM Phenotype and Complement Biosynthesis
neuroinflammation 6 ev
h-b6af8aa071
NFKB1; IKBKB; C1QA; C3proposed0.5802026-05-14Open →
36Disease-Associated Microglia (DAM) Program Drives IBA1 Downregulation
neuroinflammation 10 ev
h-298d27a24f
TREM2/TYROBPproposed0.5712026-05-14Open →
37Direct NF-κB Transcriptional Regulation of C1q Genes in Microglia
neuroinflammation 6 ev
h-0eec787493
RELA; C1QA/C1QB/C1QCproposed0.5702026-05-14Open →
38CX3CR1-Negative Trem2-High Microglial Subset Mediates Female Resilience via Est…
neuroinflammation 7 ev
h-eaee030e68
ESR1proposed0.5702026-05-14Open →
39HIF1A stabilization lowers the activation threshold of circadian-disrupted micr…
neuroinflammation 5 ev
h-15b0ade220
HIF1Aproposed0.5662026-05-14Open →
40Timed Senolytic Therapy Eliminates p16^Ink4a/p21^Cip1-Senescent Microglia to Pr…
neuroinflammation therapeutic 10 ev
h-e14a97bf
CDKN2A (p16^Ink4a), CDKN1A (p21^Cip1/Waf1)promoted0.5642026-05-14Open →
41MOG-IgG induces spinal cord demyelination through Fcγ receptor-dependent macrop…
neuroinflammation 6 ev
h-9f5ce0a588
MOG, FCGR1A, FCGR3A, FCGR2A, SYK, IRAK4proposed0.5602026-05-14Open →
42Temporal cGAS-STING Activation Stage-Specific Therapeutic Targeting
neuroinflammation 7 ev
h-cfcf4d4c0d
STING (TMEM173)proposed0.5602026-05-14Open →
43Temporal NLRP3 Inhibition During SPP1-Driven Microglial Activation Windows
neuroinflammation combination 5 ev
h-var-ce29b18697
NLRP3promoted0.5512026-05-14Open →
44Astrocytic SPP1 Modulation Through STAT3-Dependent Transcriptional Control
neuroinflammation combination 5 ev
h-var-e607efdac0
SPP1promoted0.5512026-05-14Open →
45Combined NAMPT-Alectinib Targeting of SASP-Complement Cascade
neuroinflammation 5 ev
h-292a1ec3
NAMPT, SIRT1, C1QA/C1QB/C1QC, IL1Bproposed0.5492026-05-13Open →
46SYK-Independent TREM2 Pathways Remain Functional in TYROBP Deficiency
neuroinflammation mechanistic 7 ev
h-69ce9196
SYK, TREM2promoted0.5482026-05-14Open →
47CNTF-JAK/STAT3 Reprogramming of Trained Microglia to Neuroprotective State
neuroinflammation 6 ev
h-d69f2fdd
CNTFRα/GP130 → JAK1/JAK2 → p-STAT3(Y705)proposed0.5472026-05-14Open →
48Systemic IL-6–STAT3–Hepatic C3 Axis and BBB-Mediated Complement Translocation
neuroinflammation 5 ev
h-0d030c455b
IL6; STAT3; C3proposed0.5402026-05-14Open →
49TAM Receptor (MERTK/AXL) Cross-Regulation
neuroinflammation 8 ev
h-2a43bfc5b1
MERTK, AXL, TYRO3, PROS1 (Protein S), GAS6proposed0.5402026-05-14Open →
50C1Q-Angiogenic Axis Promoting Plaque Neovascularization
neuroinflammation 8 ev
h-fcd35131cf
C1QA/C1QCproposed0.5302026-05-14Open →
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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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