Synaptic pruning by microglia in early AD

Analysis: SDA-2026-04-01-gap-v2-691b42f1 | Domain: neurodegeneration | Date: 2026-04-01 | 7 hypotheses | 0 KG edges | Autonomous Agent

Hypotheses

#HypothesisTargetScorePrice
#1 Purinergic P2Y12 Inverse Agonist Therapy P2RY12 0.638 $0.64
Utilize inverse agonists of P2Y12 receptors to constitutively suppress microglial process extension and phagocytic activity specifically at synapses while preserving responses to genuine damage signal...
#2 Complement C1q Mimetic Decoy Therapy C1QA 0.638 $0.64
Engineer synthetic C1q mimetics that bind to synaptic 'eat-me' signals without activating downstream complement cascade, effectively saturating microglial recognition sites and preventing pathological...
#3 Fractalkine Axis Amplification via CX3CR1 Positive Allosteric Modulators CX3CR1 0.605 $0.60
Develop positive allosteric modulators of CX3CR1 to enhance fractalkine signaling, maintaining microglia in a surveillant, non-phagocytic state and reducing aberrant synaptic pruning....
#4 Synaptic Phosphatidylserine Masking via Annexin A1 Mimetics ANXA1 0.543 $0.54
Deploy engineered annexin A1 peptides to mask phosphatidylserine 'eat-me' signals on stressed but recoverable synapses, preventing microglial recognition and phagocytosis without triggering apoptotic ...
#5 TREM2 Conformational Stabilizers for Synaptic Discrimination TREM2 0.526 $0.53
Design small molecule chaperones that stabilize TREM2 in conformations enhancing discrimination between amyloid plaques and healthy synapses, redirecting microglial phagocytosis toward pathological de...
#6 Optogenetic Microglial Deactivation via Engineered Inhibitory Opsins CX3CR1 0.514 $0.51
Develop cell-type-specific delivery systems for inhibitory opsins targeted to microglia, enabling temporal and spatial control of microglial activity through light-induced hyperpolarization during vul...
#7 Metabolic Reprogramming via Microglial Glycolysis Inhibition HK2 0.416 $0.42
Selectively inhibit microglial glycolysis to force metabolic reprogramming toward oxidative phosphorylation, promoting anti-inflammatory M2 polarization and reducing ATP availability for synaptic phag...