Oxidative Stress and Gut-Derived Lipopolysaccharides in Neurodegenerative Disease: Role of NOX2

BACKGROUND: Neurodegenerative diseases (ND) as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis represent a growing cause of disability in the developed countries. The underlying physiopathology is still unclear. Several lines of evidence suggest a role for oxidative stress and NADPH oxidase 2 (NOX2) in the neuropathological pathways that lead to ND. Furthermore, recent studies hypothesized a role for gut microbiota in the neuroinflammation; in particular, lipopolysaccharide (LPS) derived from Gram-negative bacteria in the gut is believed to play a role in causing ND by increase of oxidative stress and inflammation. The aim of this study was to assess NOX2 activity as well as serum 8-iso-prostaglandin F2α (8-iso-PGF2α (8-iso-PGF2 METHODS: One hundred and twenty-eight consecutive subjects, including 64 ND patients and 64 controls (CT) matched for age and gender, were recruited. A cross-sectional study was performed to compare serum activity of soluble NOX2-dp (sNOX2-dp), blood levels of isoprostanes, serum H(2)O(2), and LPS in these two groups. Serum zonulin was used to assess gut permeability. RESULTS: Compared with CT, ND patients had higher values of sNOX2-dp, 8-iso-PGF2α (8-iso-PGF2p < 0.001), zonulin (Rs = 0.411; p < 0.001), zonulin (Rs = 0.411; p < 0.001), zonulin (Rs = 0.411; α (8-iso-PGF2p < 0.001), zonulin (Rs = 0.411; p < 0.001), zonulin (Rs = 0.411; α (8-iso-PGF2p < 0.001), zonulin (Rs = 0.411; β, 0.459; p < 0.001), zonulin (Rs = 0.411; α (8-iso-PGF2β, 0.459; p < 0.001), zonulin (Rs = 0.411; R(2) = 57%). CONCLUSION: This study provides the first report attesting that patients with ND have high NOX2 activation that could be potentially implicated in the process of neuroinflammation.