Resolve: Microglial TREM2-SYK Pathway Enhancement

Challenge generated from hypothesis h-48858e2a (composite_score=0.798). Target gene/pathway: TREM2. Source hypothesis: Microglial TREM2-SYK Pathway Enhancement. ## Falsifiable Predictions 1. SYK activator (e.g. SC-1) increases TREM2-dependent amyloid-beta phagocytosis by >50% in primary microglia without increasing cytokine release (IL-1β, TNF-α < 1.5x baseline). 2. SYK-KO microglia are non-responsive to TREM2 agonist-stimulated phagocytosis (confirming SYK as obligate mediator; <10% increase vs >50% in SYK-WT). 3. AL002c + SYK activator combination reduces amyloid plaque load (4G8 staining) by >45% vs vehicle in 5xFAD mice at 6 months. 4. Microglial homeostatic index (TMEM119/SYK ratio) normalises to WT levels (>80% recovery) in 5xFAD TREM2-R47H knock-in mice treated with SYK activator.

$500
OPEN
Confidence:
50%
Created: 2026-04-27

Linked Targets (1)

TREM2 Triggering receptor expressed on myeloid cells 2 PDB:5UD70.63
🧬 View 3D Structure — PDB 5UD7 click to expand

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Detected Targets:
TREM2TNF

3D Protein Structure

View 3D structure: TREM2 — PDB 6YXY

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

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Linked Hypotheses (1)

Microglial TREM2-SYK Pathway Enhancement TREM20.80