NADPH-oxidases (NOX) catalyze the formation of reactive oxygen species (ROS), which play a role in the development of neurological diseases, particularly those generated by the phagocytic isoform NOX2. Increased ROS has been observed in the amyotrophic lateral sclerosis (ALS) SOD1 transgenic mouse, and in this preclinical model the inactivation of NOX2 decreases ROS production and extends survival. Our aim was to evaluate NOX2 activity measuring neutrophil oxidative burst in a cohort of 83 ALS patients, and age- and gender-matched healthy controls. Oxidative burst was measured directly in fresh blood using Phagoburst™ assay by flow cytometry. Mean fluorescence intensity (MFI), emitted in response to different stimuli, leads to produce ROS and corresponds to the percentage of oxidizing cells and their enzymatic activity (GeoMean). No difference was found between the MFI values in cases and controls. NOX2 activity was independent from gender and age, and in patients was not related to disease duration, site of onset (bulbar vs. spinal), or ALSFRS-R score. However, patients with a NOX2 activity lower than the median value showed a 1-year increase of survival from onset (p = 0.011). The effect of NOX2 was independent from other known prognostic factors. These findings are in keeping with the observations in the mouse model of ALS, and demonstrate the strong role of NOX2 in modifying progression in ALS patients. A proper modulation of NOX2 activity might hold therapeutic potential for ALS.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s00415-014-7470-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Klebsiella pneumoniae-derived extracellular vesicles impair endothelial function by inhibiting SIRT1.
Cell Commun Signal
January 2025
Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling Cardiovascular Diseases, Ministry of Education; Collaborative Innovation Center for Cardiovascular Disorders, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, 100029, China.
Background: The potential role of Klebsiella pneumoniae (K.pn) in hypertension development has been emphasized, although the specific mechanisms have not been well understood. Bacterial extracellular vesicles (BEVs) released by Gram-negative bacteria modulate host cell functions by delivering bacterial components to host cells.
View Article and Find Full Text PDFDietary blueberry before and/or after exposure to HZE particle radiation attenuates neuroinflammation, oxidative stress, glial cell activation, and memory deficits in rats.
J Nutr
January 2025
USDA-ARS, Jean Mayer Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. Electronic address:
Background: Acute neuroinflammatory and oxidative-stress (OS)-inducing stressors, such as high energy and charge (HZE) particle irradiation, produce accelerated aging in the brain. Anti-inflammatory and antioxidant foods, such as blueberries (BB), attenuate neuronal and cognitive deficits when administered to rodents before or both before and after HZE particle exposure. However, the effects of post-stressor treatments are unknown and may be important to repair initial damage and prevent progressive neurodegeneration.
View Article and Find Full Text PDFDectin-2 depletion alleviates osteoclast-induced bone loss in periodontitis via Syk/NOX2/ROS signaling.
Free Radic Biol Med
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University. Electronic address:
Periodontitis is the sixth most common disease worldwide and is closely associated with various systemic diseases, impacting overall health. It is characterized by the over-differentiation and activity of osteoclasts, leading to increased bone resorption and subsequent bone loss. Current treatments for bone loss are not ideal, highlighting the need for new targeted therapeutic strategies.
View Article and Find Full Text PDFRenal tubular S100A7a impairs fatty acid oxidation and exacerbates renal fibrosis via both intracellular and extracellular pathway.
Biochim Biophys Acta Mol Basis Dis
January 2025
State Key Laboratory of Organ Failure Research, National Clinical Research Center of Kidney Disease, Guangdong Provincial Institute of Nephrology, Guangdong Provincial Key Laboratory of Renal Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China; Biobank of Peking University First Hospital, Peking University First Hospital, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University Health Science Center, Peking University, Beijing 100034, China. Electronic address:
A couple of S100 family proteins (S100s) have been reported to exert pro-inflammatory functions in the progression of renal fibrosis (RF). Unlike some S100s which are expressed by both epithelial and stromal inflammatory cells, S100A7 is restricted expressed in epithelium. Persistent S100A7 expression occurs in some invasive carcinomas and is associated with poor prognostic factors.
View Article and Find Full Text PDFNPA7: A Dual Receptor Activating Peptide That Inhibits Cardiac Oxidative Stress.
Hypertension
January 2025
Cardiorenal Research Laboratory, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. (Xiaoyu Ma, J.C.M., D.G.M., Xiao Ma, Y.Z., S.P., Y.W., S.J.S., J.C.B.).
Background: Cardiomyocyte oxidative stress significantly contributes to the progression of hypertension-induced heart failure, highlighting the need for targeted therapies. We developed a novel peptide, NPA7, that coactivates the GC-A (guanylyl cyclase A)/cGMP and MasR (Mas receptor)/cAMP pathway. This study aimed to test NPA7's ability to inhibit oxidative stress by modulating the p62-KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2-related factor 2) pathway in human cardiomyocytes (HCMs) and a rat model of hypertension.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!