Fig. 1.

The mechanisms of neuronal dysfunction caused by HIV-1, cART, and drug abuse. Although HIV-1 cannot infect neuron itself, specific HIV viral proteins including envelope glycoprotein (gp)120, gp41, gp 160, Nef, Rev, TAT, and Vpr and inflammatory factors secreted from HIV-1-infected CNS macrophages, microglia, and astrocytes which can cause synaptodendritic damage in neurons leading to HIV-1-associated neuropathogenesis; drug abuse and cART could directly induce synaptodendritic injury and indirectly alter neuronal morphology and functions by modulating the glial cells in the CNS; the neurocognitive impairment or synaptic injury was found in HIV-transgenic rats, Tat-transgenic mice, Dox-inducible Tat-transgenic mice, and HIV gp120-transgenic mice