AIDS and the brain: is there a chemokine connection?

Many HIV-1-positive individuals suffer from a variety of neurological probl ems known collectively as the HIV-1-related cognitive-motor complex. Howeve r, the molecular mechanisms that underlie HIV-1-induced neuropathology are unclear. They might include a combination of indirect effects, which result from the release of neurotoxins from activated astrocytes and microglia, a nd the direct effects of HIV-1-related proteins, such as gp120, on neurons. As the interaction of gp120 with immune cells has been shown to require th e participation of chemokine receptors, this article explores the possibili ty that such receptors participate in the events underlying HIV-1-induced n europathology. It is now clear that many types of cell in the brain possess chemokine receptors, including microglia, glia and neurons,and the interac tion of gp120 with neuronal chemokine receptors initiates apoptotic death o f neurons in vitro. Such effects might be modified by the actions of chemok ines that act at these same receptors. However, the importance of this dire ct interaction with neurons in vivo and its relevance in the pathogenesis o f AIDS-related dementia still needs to be established. Furthermore, the exi stence of chemokine receptors on neurons suggests that chemokines might reg ulate neuronal functions physiologically.