Exploitation of the HIV-1 coat glycoprotein, gp120, in neurodegenerative studies in vivo

Neuronal loss has often been described at post-mortem in the brain neocorte x of patients suffering from AIDS. Neuroinvasive strains of HIV infect macr ophages, microglial cells and multinucleated giant cells, but not neurones. Processing of the virus by cells of the myelomonocytic lineage yields vira l products that, in conjunction with potentially neurotoxic molecules gener ated by the host, might initiate a complex network of events which lead neu rones to death. In particular, the HIV-1 coat glycoprotein, gp120, has been proposed as a likely aetiologic agent of the described neuronal loss becau se it causes death of neurones in culture. More recently, it has been shown that brain neocortical cell death is caused in rat by intracerebroventricu lar injection of a recombinant gp120 coat protein, and that this occurs via apoptosis. The latter observation broadens our knowledge in the pathophysi ology of the reported neuronal cell loss and opens a new lane of experiment al research for the development of novel therapeutic strategies to limit da mage to the brain of patients suffering from HIV-associated dementia.