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.

journal_name

Free Radic Res

journal_title

Free radical research

authors

Cecarini V,Ding Q,Keller JN

doi

10.1080/10715760701286159

subject

Has Abstract

pub_date

2007-06-01 00:00:00

pages

673-80

issue

6

eissn

1071-5762

issn

1029-2470

pii

778898565

journal_volume

41

pub_type

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