Vol. 114, No. 12 EnvironewsOpen AccessHeadliners: Neurodegenerative Disease: Inflammatory Enzyme Modulates Motor Neuron Damage in Amyotrophic Lateral Sclerosis Jerry Phelps Jerry Phelps Search for more papers by this author Published:1 December 2006https://doi.org/10.1289/ehp.114-a697Cited by:1AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit Wu DC, Ré DB, Nagai M, Ischiropoulos H, Przedborski S. 2006. The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice. Proc Natl Acad Sci U S A 103:12132–12137.Approximately 30,000 patients in the United States currently have amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. ALS is a progressive neuromuscular disease that weakens and eventually destroys motor neurons that connect the brain with the skeletal muscles. NIEHS grantee Serge Przedborski of Columbia University has pioneered the investigation of the molecular mechanisms leading to the death of neurons that occurs in ALS and Parkinson disease. Now Przedborski and colleagues provide new insights into the role of the enzyme NADPH oxidase in the death of motor neurons as a result of ALS.ALS, the most common adult-onset paralytic disease, is most commonly diagnosed in middle age, and affects men more often than women. Patients gradually lose the ability to speak, swallow, and move voluntarily. Sensory function and intellectual ability are unaffected, and death usually results from loss of respiratory function. The disease affects all racial, socioeconomic, and ethnic groups, and the life expectancy of ALS patients is usually three to five years after diagnosis.In this study, the investigators observed spinal cord tissue using a mouse histochemistry model, and created a timeline chronicling observed motor abnormality behavior in transgenic SOD1G93A mice. They also conducted histological evaluations of postmortem human tissue using a control group and an ALS group.The researchers discovered that the NADPH oxidase enzyme, an important component in the generation of destructive reactive oxygen species during inflammation, is active in the spinal cords of ALS patients and also in the mouse model of the disease. When they inactivated the enzyme in the mice, they found that neurodegeneration was significantly delayed, and the mice lived longer. Additional studies also showed that NADPH oxidase–derived oxidative products also damaged proteins including insulin-like growth factor 1 receptors located on motor neurons.Insulin-like growth factor 1 has been demonstrated to have therapeutic potential in ALS patients. The authors conclude that these results suggest that coadministration of an antiinflammatory agent with the protein may improve its efficacy in ALS patients.FiguresReferencesRelatedDetailsCited by Rundle A, Hoepner L, Hassoun A, Oberfield S, Freyer G, Holmes D, Reyes M, Quinn J, Camann D, Perera F and Whyatt R (2012) Association of Childhood Obesity With Maternal Exposure to Ambient Air Polycyclic Aromatic Hydrocarbons During Pregnancy, American Journal of Epidemiology, 10.1093/aje/kwr455, 175:11, (1163-1172), Online publication date: 1-Jun-2012. Vol. 114, No. 12 December 2006Metrics About Article Metrics Publication History Originally published1 December 2006Published in print1 December 2006 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.