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NADPH-oxidase activation and cognition in Alzheimer disease progression
- Source :
- Free Radical Biology and Medicine. 51:171-178
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Superoxide production via NADPH-oxidase (NOX) has been shown to play a role in a variety of neurological disorders, including Alzheimer disease (AD). To improve our understanding of the NOX system and cognitive impairment, we studied the various protein components of the phagocytic isoform (gp91(phox), or NOX2) in the frontal and temporal cortex of age- and postmortem-matched samples. Individuals underwent antemortem cognitive testing and postmortem histopathologic assessment to determine disease progression and assignment to one of the following groups: no cognitive impairment (NCI), preclinical AD, mild cognitive impairment (MCI), early AD, and mild-to-moderate AD. Biochemical methods were used to determine overall NOX activity as well as levels of the various subunits (gp91(phox), p67(phox), p47(phox), p40(phox), and p22(phox)). Overall enzyme activity was significantly elevated in the MCI cohort in both cortical regions compared to the NCI cohort. This activity level remained elevated in the AD groups. Only the NOX cytosolic subunit proteins (p67(phox), p47(phox), and p40(phox) ) were significantly elevated with disease progression; the membrane-bound subunits (gp91(phox) and p22(phox)) remained stable. In addition, there was a robust correlation between NOX activity and the individual's cognitive status such that as the enzyme activity increased, cognitive performance decreased. Collectively, these data show that upregulated NADPH-oxidase in frontal and temporal cortex suggests that increases in NOX-associated redox pathways might participate in early pathogenesis and contribute to AD progression.
- Subjects :
- Male
inorganic chemicals
medicine.medical_specialty
Pathology
Blotting, Western
medicine.disease_cause
Biochemistry
Article
Pathogenesis
chemistry.chemical_compound
Enzyme activator
Cognition
Downregulation and upregulation
Alzheimer Disease
Superoxides
Physiology (medical)
Internal medicine
medicine
Humans
Aged
Aged, 80 and over
Temporal cortex
Membrane Glycoproteins
NADPH oxidase
biology
Superoxide
business.industry
NADPH Oxidases
medicine.disease
Enzyme Activation
Oxidative Stress
Endocrinology
chemistry
NADPH Oxidase 2
Disease Progression
cardiovascular system
biology.protein
Female
Alzheimer's disease
business
Oxidative stress
Subjects
Details
- ISSN :
- 08915849
- Volume :
- 51
- Database :
- OpenAIRE
- Journal :
- Free Radical Biology and Medicine
- Accession number :
- edsair.doi.dedup.....58253be86312e16e3b83fce3ad33714d