title: Oxidative inactivation of the proteasome in Alzheimer's disease.
abstract: In the present study we isolated proteasome complexes from control, mild cognitive impairment (MCI), and Alzheimer's disease (AD) subjects. No significant difference in the amount of proteasomes was detected across the different groups, although impairments in chymotrypsin-like proteasome activity was observed in AD subjects. Large impairments in proteasome- mediated degradation of an oxidized protein substrate was observed in MCI and AD subjects. Incubation with a reducing agent (DTT) had no significant effect on proteasome chymotrypsin-like activity, but fully restored proteasome-mediated protein degradation in MCI and AD subjects. Proteasomes from AD subjects exhibited elevations in protein carbonyls, 4-hydroxynonenal-conjugation, and neuroprostane-conjugation. Together, these data confirm that impairments in the function of purified proteasomes occurs in the earliest stages of AD, and directly support a role for oxidative inactivation contributing to declines in proteasome function in AD.
authors.affiliation: Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cecarini
authors.forename: Qunxing
authors.initials: Q
authors.lastname: Ding
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Keller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D003072:Cognition Disorders / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000302:isolation & purification / Q000378:metabolism; D061988:Proteasome Inhibitors
chemical_list: D061988:Proteasome Inhibitors; D046988:Proteasome Endopeptidase Complex