Linked Life Data

14675732

Source:http://linkedlifedata.com/resource/pubmed/id/14675732

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-12-16
pubmed:abstractText
Converging evidence supports the role of oxidative stress in the pathology of Alzheimer's disease (AD). This notion is further supported by recent findings of increased NAD(P)H:quinone oxidodreductase (NQO1) activity, a potent antioxidant system, in association with hippocampal AD pathology. If increased NQO1 activity is truly related to the AD process, however, we would expect to see regional co-localization of NQO1 activity with AD pathology throughout affected brain regions and the absence of NQO1 activity in regions unaffected by AD. We examined this hypothesis by measuring NQO1 enzymatic activity and NQO1 immunohistochemical staining in regions commonly affected by the AD process such as frontal cortex and compared this to regions generally unaffected by the AD process such as occipital cortex, cerebellum, and substantia nigra for a group of AD patients and controls. The ratio of frontal to cerebellar NQO1 enzymatic activity was significantly increased in patients with AD (2.07 +/- 1.90) versus controls (0.60 +/- 0.31; P < 0.03). Moreover, regional immunohistochemical staining revealed specific localization of NQO1 staining to astrocytes and neurites surrounding senile plaques. The extent of immunohistochemical staining also closely correlated with the extent of local AD pathology across the various brain regions examined. Neuronal NQO1 staining seen in frontal cortex of AD patients was absent in frontal cortex of controls, but was found to the same extent in neurons of the substantia nigra of both AD patients and controls. We conclude that NQO1 activity co-localizes closely with AD pathology supporting a presumed role as an antioxidant system upregulated in response to the oxidative stress of the AD process. The antioxidant role for NQO1 is further supported by finding increased neuronal NQO1 activity in substantia nigra neurons of both AD patients and controls as this neuronal population is known to be under constant oxidative stress. While requiring further study, these findings, in conjunction with previous work, suggest that increased NQO1 activity may be neuroprotective, may offer novel insights into the pathophysiology of AD and may also provide possible avenues for future treatment.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0197-4580
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
63-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Regional NAD(P)H:quinone oxidoreductase activity in Alzheimer's disease.
pubmed:affiliation
Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, KS 66160, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.