Tumor necrosis factor-α (TNFα) is a prototypic inflammatory cytokine up-regulated in most if not all neurodegenerative diseases. Many studies have reported variable roles in the adult or pathological brain. In contrast, the implication of TNFα in developmental neuronal cell death has been well documented in few studies. In sympathetic and trigeminal neurons, TNFα acts in an autocrine manner to induce immediate cell death on neurotrophic factor deprivation. In the spinal cord, TNFα is transiently produced by macrophages and commits motoneurons to become competent to die 2 days later. TNFα is also likely to induce immediate and delayed prodeath effects in adult and pathological tissues. Data obtained in embryonic systems will thus help to develop new therapeutic approaches to pathological neuronal death in adults.
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