Dual CD73/A2AR blockade modulates the neurotoxic astrocyte phenotype without disrupting core inflammatory signaling

IntroductionExcessive activation of the adenosine A2A receptor (A2AR) contributes to chronic neuroinflammation, in part through spatial coupling with the adenosine-generating enzyme CD73, which enables localized adenosine signaling. Coordinated regulation of Nt5e and Adora2a across neuropathological conditions supports dual targeting of the CD73/A2AR axis to constrain maladaptive inflammatory signaling.MethodsPrimary rat astrocytes were exposed to TNF-α, IL-1α, and C1q (TIC) to induce a neurotox