Neuroprotective and toxic changes in microglia in neurodegenerative disease.

Microglia are macrophage-like cells in the CNS. As macrophages, activated microglia remove potentially deleterious debris and promote tissue repair. However, they can release potentially cytotoxic substances in vitro. So-called fully activated microglia, observed at the injury site in many neurodegenerative conditions, are neurotoxic. This suggests that some factor(s) may contribute to change microglial phenotype from protective to toxic, but details are not clear. Recently, we generated HIV-derived Nef protein-transduced microglia. They increase the potential to produce O(-)(2) and MPO-like peroxidase activity, resulting in neurotoxicity. Therefore, the target protein(s) of Nef might be involved in the control of microglial neurotoxicity.