title: Quinone reductase (NQO1), a sensitive redox indicator, is increased in Alzheimer's disease.
abstract: NAD(P)H:quinone oxidoreductase 1 (NQO1), a redox-regulated flavoenzyme, plays a central role in monitoring cellular redox state. NQO1 acts to protect against oxidative stress induced by a variety of metabolic situations, including metabolism of quinones and other xenobiotics, by: (i) functioning as a two electron donor to provide a shunt that competes with the formation of reactive oxygen species; (ii) maintaining reduced coenzyme Q; and (iii) regulating the stress activated kinase pathway. In Alzheimer's disease, while there is abundant evidence for the involvement of oxidative stress, the cause or the consequences are largely unresolved. We suspected that increased NQO1 could signal a major shift in redox balance in Alzheimer's disease and, in this study, found that NQO1 is localized not only to neurofibrillary tangles but also the cytoplasm of hippocampal neurons. By marked contrast, there is very little NQO1 in the same neuronal populations in young and age-matched controls. This novel association of NQO1 further buttresses the nexus of oxidative stress, via free radicals, with selective neuronal vulnerability and also supports a fundamental abnormality in redox balance in Alzheimer's disease.
authors.affiliation: Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Raina
authors.forename: D J
authors.initials: DJ
authors.lastname: Templeton
authors.forename: J C
authors.initials: JC
authors.lastname: Deak
authors.forename: G
authors.initials: G
authors.lastname: Perry
authors.forename: M A
authors.initials: MA
authors.lastname: Smith
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D006801:Humans; D018384:Oxidative Stress; D011808:Quinone Reductases / Q000096:biosynthesis* / Q000276:immunology
chemical_list: C041831:NADH dehydrogenase (quinone); D011808:Quinone Reductases