Chemokine receptors and neurotrophic factors: potential therapy against aids dementia?
Chemokine receptors, in particular, CXCR4 and CCR5, mediate human immunodeficiency virus type 1 (HIV-1) infection of immunocompetent cells and the apoptosis of these cells. However, the virus does not infect neurons. Yet through a variety of mechanisms, HIV promotes glial cell activation, synaptodendritic alterations, and neuronal loss that ultimately lead to motor and cognitive impairment. Chemokines and chemokine receptors are abundant in the adult central nervous system and play a role in neuronal apoptosis evoked by HIV proteins. Thus, reducing the availability of chemokine receptors may prevent the neuronal degeneration seen in HIV-positive patients. In this article, we present and discuss a recent experimental approach aimed at testing effective neuroprotective therapies against HIV-mediated neuronal degeneration.
Mocchetti
Italo
I
Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA. moccheti@georgetown.edu
Bachis
Alessia
A
Masliah
Eliezer
E
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D009410:Nerve Degeneration / Q000517:prevention & control* / Q000821:virology; D009414:Nerve Growth Factors / Q000627:therapeutic use*; D019707:Receptors, Chemokine / Q000378:metabolism*
D018925:Chemokines; D009414:Nerve Growth Factors; D019707:Receptors, Chemokine