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.