In the present study, we further found that KYNA was able to block α7nAChR/NF-κB signaling to promote A2 (neuroprotective) astrocyte generation, which enhances neurotrophic factor secretion and reduces glutamatergic toxicity, leading to amelioration of neurological damage and cognitive deficits in HAND. The gene discussed is NFKB1; the disease is HIV-associated neurocognitive disorder.