Tumor necrosis factor-α at the crossroads of neuronal life and death during HIV-associated dementia

Human immunodeficiency type-1 (HIV-1) infection is known to cause disorders of the CNS, including HIV-associated dementia (HAD). It is suspected that tumor necrosis factor-alpha (TNF-alpha) released by infected microglia and macrophages play a role in neuronal injury seen in HAD patients. Accordingly, studies suggest that the level of TNF-alpha mRNA increases with increasing severity of dementia in patients, and that inhibitors of TNF-alpha release reduces neuronal injury in murine model of HAD. However, the exact role of TNF-alpha in relation to neuronal dysfunction is a matter of ongoing debate. One school of thought hails TNF-alpha as the inducer and mediator of neurodegeneration and their evidence suggest that TNF-alpha kill neurons directly by recruiting caspases or may kill indirectly by various means. In sharp contrast to this, another concept theory envisages a role for TNF-alpha in negotiating neuroprotection during HAD. The current compilation examines these contradictory concepts, and evaluates their efficacy in the light of TNF-alpha signaling. It also attempts to elaborate the current consensus outlook of TNF-alpha's role during HAD.