Composite
66%
Novelty
64%
Feasibility
74%
Impact
66%
Mechanistic
74%
Druggability
54%
Safety
57%
Confidence
58%

Mechanistic description

NF-kB suppression in glia decreases ectonucleotidase and cytokine programs that sustain extracellular adenosine, indirectly reducing ADORA2A pathway output in mood circuits.

Evidence for (6)

  • Inflammatory adenosine tone offers a receptor-linked but indirect route to specificity.

  • NF-κB signaling in inflammation and cancer.

    PMID:34977871 2021 MedComm (2020)
  • Brain Specific RagA Overexpression Triggers Depressive-Like Behaviors in Mice via Activating ADORA2A Signaling Pathway.

    PMID:39373701 2024 Adv Sci (Weinh)
  • Structural studies of NF-κB signaling.

    PMID:21135870 2011 Cell Res
  • Inactivation of adenosine receptor 2A suppresses endothelial-to-mesenchymal transition and inhibits subretinal fibrosis in mice.

    PMID:38446902 2024 Sci Transl Med
  • Regulation of NF-kappaB function.

    PMID:16626297 2006 Biochem Soc Symp

Evidence against (1)

  • Mood benefit might arise from broader anti-inflammatory effects without ADORA2A dependence.