GSK3β-activation is a point of convergence for HIV-1 and opiate-mediated interactive neurotoxicity.

摘要: Infection of the CNS with HIV-1 occurs rapidly after primary peripheral infection. can induce a wide range neurological deficits, collectively known as HIV-1-associated neurocognitive disorders. Our previous work has shown that selected neurotoxic effects induced by individual viral proteins, Tat and gp120, HIV+ supernatant are enhanced co-exposure to morphine. This mimics co-morbid observed in opiate-abusing patients. Although there is correlation between opiate drug abuse progression disorders, mechanisms underlying interactions opiates remain obscure. Previous studies have induces through abnormal activation GSK3β. Interestingly, expression GSK3β be elevated brains young abusers indicating also linked neuropathology seen Thus, we hypothesize point convergence for HIV- opiate-mediated interactive effects. Neuronal cultures were treated from HIV-1SF162-infected THP-1 cells, presence or absence morphine inhibitors. results show inhibitors, including valproate small molecule significantly reduce HIV-1-mediated outcomes, negate result cell death, suggesting GSK3β-activation an important potential therapeutic target deficits.