[Pathogenesis of HIV-1-associated-neurologic diseases]

The neurologic disease most frequently seen during acquired immunodeficiency syndrome (AIDS) is AIDS dementia complex (ADC) or HIV encephalopathy, which is a direct consequence of HIV-1 infection of the central nervous system (CNS). A limited expression of HIV-1 in CNS and peripheral nervous system (PNS) tissue of AIDS patients in contrast to widespread functional and pathologic abnormalities suggests indirect or immunopathogenetic mechanisms of ADC and HIV-1-associated predominantly sensory neuropathy. Proposed mechanisms include injury of oligodendrocytes by tumor necrosis factor-alpha (TNF-alpha) released from macrophages, calcium dependent excitoneurotoxicity induced by gp120 HIV-1 envelope protein, N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity by quinolinic acid, cell injury by HIV-1-specific cytotoxic T cells, and apoptosis of oligodendrocytes or neurons. The amplification of cellular activation by cytokine network and cell-to-cell contact between activated macrophages and neural cells by upregulation of adhesion molecules dramatically enhance toxic effect of macrophage products.