An increase in the expression of the proinflammatory cytokine tumor necrosis factor ␣ (TNF-␣) has been observed in patients with amyotrophic lateral sclerosis (ALS) and in the mice models of the disease. TNF-␣ is a potent activator of macrophages and microglia and, under certain conditions, can induce or exacerbate neuronal cell death. Here, we assessed the contribution of TNF-␣ in motor neuron disease in mice overexpressing mutant superoxide dismutase 1 (SOD1) genes linked to familial ALS.

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... was accomplished by the generation of mice expressing SOD1 G37R or SOD1 G93A mutants in the context of TNF-␣ gene knock out. Surprisingly, the absence of TNF-␣ did not affect the lifespan or the extent of motor neuron loss in SOD1 transgenic mice. These results provide compelling evidence indicating that TNF-␣ does not directly contribute to motor neuron degeneration caused by SOD1 mutations.