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 F2 (8-iso-PGF2 (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 HO, 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-PGF2 (8-iso-PGF2 < 0.001), zonulin (Rs = 0.411; < 0.001), zonulin (Rs = 0.411; < 0.001), zonulin (Rs = 0.411; (8-iso-PGF2 < 0.001), zonulin (Rs = 0.411; < 0.001), zonulin (Rs = 0.411; (8-iso-PGF2 < 0.001), zonulin (Rs = 0.411; , 0.459; < 0.001), zonulin (Rs = 0.411; (8-iso-PGF2, 0.459; < 0.001), zonulin (Rs = 0.411; = 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.