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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice.

ALS is a fatal paralytic disorder characterized by a progressive loss of spinal cord motor neurons. Herein, we show that NADPH oxidase, the main reactive oxygen species-producing enzyme during inflammation, is activated in spinal cords of ALS patients and in spinal cords in a genetic animal model of this disease. We demonstrate that inactivation of NADPH oxidase in ALS mice delays neurodegeneration and extends survival. We also show that NADPH oxidase-derived oxidant products damage proteins such as insulin-like growth factor 1 (IGF1) receptors, which are located on motor neurons. Our in vivo and in vitro data indicate that such an oxidative modification hinders the IGF1/Akt survival pathway in motor neurons. These findings suggest a non-cell-autonomous mechanism through which inflammation could hasten motor neuron death and contribute to the selective motor neuronal degeneration in ALS.[1]

References

  1. The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice. Wu, D.C., Ré, D.B., Nagai, M., Ischiropoulos, H., Przedborski, S. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
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