🧪 Hypotheses

mechanistic 0.83

IL-6 Trans-Signaling Blockade at the Oligodendrocyte-Microglia Interface

🧬 IL6R, IL6 🏥 neuroinflammation 📖 29🏛 1

✅ 0.72 ✨ 0.65 💥 0.80

## Mechanistic Overview...

unknown 0.82

STING Antagonists as ALS Therapeutics: Drug Repurposing

🧬 STING (TMEM173) 🏥 neuroinflammation 📖 13🏛 1

✅ 0.82 ✨ 0.55 💥 0.78

## **Molecular Mechanism and Rationale**...

mechanistic 0.78

PDE4 Inhibition as Inflammatory Reset for PD Oligodendrocytes

🧬 PDE4A, PDE4B, PDE4D 🏥 neuroinflammation 📖 13🏛 1

✅ 0.62 ✨ 0.58 💥 0.75

## Mechanistic Overview...

unknown 0.76

TREM2 Crosstalk and Synergistic Activation of Phagocytic Transcriptome

🧬 TREM2/DAP12 (TYROBP) 🏥 neuroinflammation 📖 0🏛 1

✅ 0.80 ✨ 0.65 💥 0.85

**Molecular Mechanism and Rationale**...

combination 0.75

Temporal SPP1 Inhibition During Critical Windows

🧬 SPP1 🏥 neuroinflammation 📖 8🏛 1

✅ 0.70 ✨ 0.75 💥 0.80

## Mechanistic Overview...

unknown 0.74

Peripheral Monocyte/Macrophage Infiltration Mimicking Microglial Loss

🧬 CCR2 🏥 neuroinflammation 📖 8🏛 1

✅ 0.72 ✨ 0.65 💥 0.70

**Molecular Mechanism and Rationale**...

mechanistic 0.74

Aryl Hydrocarbon Receptor (AHR) Activation in B Cells Determines AQP4 Tolerance Fate

🧬 AHR, IL10, TNFRSF13B, TIGIT, FOXP3 🏥 neuroinflammation 📖 12🏛 1

✅ 0.60 ✨ 0.85 💥 0.72

**Molecular Mechanism and Rationale**...

unknown 0.72

Regional TREM2-Dependent Lipid Metabolism Determines Cortical Vulnerability in Alzheimer's Disease

🧬 TREM2 🏥 neuroinflammation 📖 0🏛 1

✅ 0.60 ✨ 0.55 💥 0.80

## Mechanistic Overview...

unknown 0.71

TGF-β1–SMAD2/3 Axis as Master Suppressor of Microglial Trained Immunity

🧬 TGFBR1/TGFBR2 → SMAD4 → SMAD2/3 🏥 neuroinflammation 📖 0🏛 1

✅ 0.68 ✨ 0.62 💥 0.72

Astrocyte-derived TGF-β1 engages microglial TGFBRII/TGFBRI complex, activating SMAD2/3 corepressor complexes that displace RelA/p300 coactivators at N...

unknown 0.68

PGE2–EP2–cAMP–PKA Axis Displaces Pathological Microglial Memory Traces

🧬 PTGER2 (EP2) → ADCY → cAMP → PRKA (PKA) → SIRT1 🏥 neuroinflammation 📖 8🏛 1

✅ 0.70 ✨ 0.68 💥 0.65

Astrocyte-produced PGE2 (via COX2 induction) engages microglial EP2 receptors, elevating cAMP and activating PKA. PKA phosphorylates NF-κB p65(S276), ...

unknown 0.68

Autophagy-Lysosomal Degradation of IBA1 in Stressed Microglia

🧬 LC3/P62/SQSTM1 🏥 neuroinflammation 📖 0🏛 1

✅ 0.75 ✨ 0.72 💥 0.68

## Mechanistic Overview...

combination 0.68

NLRP3/Mitophagy Coupling Modulation

🧬 NLRP3 🏥 neuroinflammation 📖 15🏛 1

✅ 0.80 ✨ 0.70 💥 0.85

## Mechanistic Overview...

unknown 0.66

Chronic cGAS/STING Hyperactivation Drives Progressive Neurodegeneration Through Sustained Type I Interferon Signaling

🧬 cGAS (CGAS) / STING (TMEM173) / IFNAR1/2 🏥 neuroinflammation 📖 0🏛 1

✅ 0.68 ✨ 0.72 💥 0.75

## Mechanistic Overview...

unknown 0.66

Astrocyte IL-1β as Paracrine Mediator of Microglial Complement Expression

🧬 IL1B; IL1R1; MYD88 🏥 neuroinflammation 📖 0🏛 1

✅ 0.72 ✨ 0.55 💥 0.78

**Molecular Mechanism and Rationale**...

combination 0.65

C3aR Blockade Disrupts the Microglial-Astrocyte Feedforward Neurotoxic Loop

🧬 C3AR1, C3, NFKB1 🏥 neuroinflammation 📖 13🏛 1

✅ 0.58 ✨ 0.72 💥 0.75

## **Molecular Mechanism and Rationale**...

combination 0.65

IL-10-Producing B10 Cells Establish AQP4-Specific Peripheral Tolerance Through Macrophage Reprogramming

🧬 IL10, CSF1R, CD40 🏥 neuroinflammation 📖 10🏛 1

✅ 0.55 ✨ 0.80 💥 0.78

## Mechanistic Overview...

unknown 0.64

Epigenetic Silencing of AIF1 Gene Locus by Chronic Inflammation

🧬 DNMT1/DNMT3A 🏥 neuroinflammation 📖 0🏛 1

✅ 0.65 ✨ 0.82 💥 0.75

## **Molecular Mechanism and Rationale**...

unknown 0.63

Liver-Derived Inflammatory Suppressors Downregulate Microglial IBA1

🧬 STAT3/JAK1 🏥 neuroinflammation 📖 0🏛 1

✅ 0.68 ✨ 0.55 💥 0.72

## Mechanistic Overview...

unknown 0.63

C1Q-Triggered NLRP3 Inflammasome Assembly in Plaque Macrophages

🧬 C1QA/C1QC 🏥 neuroinflammation 📖 0🏛 1

✅ 0.72 ✨ 0.58 💥 0.68

**Molecular Mechanism and Rationale**...

unknown 0.62

C1Q-Induced Foam Cell Formation via Scavenger Receptor Upregulation

🧬 C1QA/C1QC 🏥 neuroinflammation 📖 0🏛 1

✅ 0.70 ✨ 0.62 💥 0.72

## Mechanistic Overview...

unknown 0.62

Metabolic Rewiring via SPP1-Induced HIF1α Glycolytic Shift

🧬 HIF1A (HIF1α), MTOR (mTORC1), EGLN1 (PHD2) 🏥 neuroinflammation 📖 0🏛 1

✅ 0.65 ✨ 0.80 💥 0.58

**Molecular Mechanism and Rationale**...

unknown 0.61

Age-Accelerated miR-155 Upregulation Primes Nigral Microglia for Parkinson's Disease Pathology

🧬 miR-155 🏥 neuroinflammation 📖 0🏛 1

✅ 0.55 ✨ 0.70 💥 0.65

## Mechanistic Overview...

unknown 0.61

Microglial priming is primarily epigenetic, with metabolic changes acting as coupled consequences or cofactors

🧬 KDM6B 🏥 neuroinflammation 📖 0🏛 1

✅ 0.66 ✨ 0.50 💥 0.67

## Mechanistic Overview...

therapeutic 0.60

STING Antagonism Prevents Acute-to-Chronic Neuroinflammation Transition via Interruption of IFN-I Feedback Looping

🧬 TMEM173 (STING) 🏥 neuroinflammation 📖 10🏛 1

✅ 0.52 ✨ 0.82 💥 0.78

## Mechanistic Overview...

unknown 0.60

TNF-α–C1r/C1s Bridge Between NF-κB and Classical Complement Cascade

🧬 TNF; TNFRSF1A; C1R; C1S 🏥 neuroinflammation 📖 0🏛 1

✅ 0.62 ✨ 0.60 💥 0.70

**Molecular Mechanism and Rationale**...

unknown 0.60

C1Q-Mediated Defective Efferocytosis Driving Necrotic Core Expansion

🧬 C1QA/C1QC 🏥 neuroinflammation 📖 0🏛 1

✅ 0.68 ✨ 0.55 💥 0.65

## Mechanistic Overview...

unknown 0.60

APOE4 Induces Region-Specific Microglial Senescence Driving Frontal Cortex Neurodegeneration

🧬 APOE4 🏥 neuroinflammation 📖 0🏛 1

✅ 0.50 ✨ 0.82 💥 0.72

## Mechanistic Overview...

combination 0.60

Aryl Hydrocarbon Receptor (AhR) Activation by Microbiome Metabolites Promotes A2 Polarization

🧬 AHR, CYP1A1, NFKB1, IL6 🏥 neuroinflammation 📖 11🏛 1

✅ 0.45 ✨ 0.85 💥 0.72

## Mechanistic Overview...

unknown 0.60

Selective C1q-CRP vs. C1q-IgG Axis Inhibition

🧬 C1QA/C1QB/C1QC, CRP, FCGR1A 🏥 neuroinflammation 📖 4🏛 1

✅ 0.50 ✨ 0.65 💥 0.75

## Mechanistic Overview...

unknown 0.59

Astrocyte-Derived EV miR-146a-5p Mimics as Erasers of Trained Microglial NF-κB Memory

🧬 miR-146a-5p → IRAK1, TRAF6, NOTCH1, HDAC1 🏥 neuroinflammation 📖 0🏛 1

✅ 0.42 ✨ 0.75 💥 0.60

AEVs containing miR-146a-5p are taken up by microglia and suppress IRAK1/TRAF6, disrupting sustained NF-κB activation that maintains pathological memo...