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Oxidative inactivation of the proteasome in Alzheimer's disease.
Free Radic Res 2007; 41(6):673-80FR

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+Show Affiliations

Sanders Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17516240

Citation

Cecarini, Valentina, et al. "Oxidative Inactivation of the Proteasome in Alzheimer's Disease." Free Radical Research, vol. 41, no. 6, 2007, pp. 673-80.
Cecarini V, Ding Q, Keller JN. Oxidative inactivation of the proteasome in Alzheimer's disease. Free Radic Res. 2007;41(6):673-80.
Cecarini, V., Ding, Q., & Keller, J. N. (2007). Oxidative inactivation of the proteasome in Alzheimer's disease. Free Radical Research, 41(6), pp. 673-80.
Cecarini V, Ding Q, Keller JN. Oxidative Inactivation of the Proteasome in Alzheimer's Disease. Free Radic Res. 2007;41(6):673-80. PubMed PMID: 17516240.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidative inactivation of the proteasome in Alzheimer's disease. AU - Cecarini,Valentina, AU - Ding,Qunxing, AU - Keller,Jeffrey N, PY - 2007/5/23/pubmed PY - 2007/8/8/medline PY - 2007/5/23/entrez SP - 673 EP - 80 JF - Free radical research JO - Free Radic. Res. VL - 41 IS - 6 N2 - 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. SN - 1071-5762 UR - https://www.unboundmedicine.com/medline/citation/17516240/Oxidative_inactivation_of_the_proteasome_in_Alzheimer's_disease_ L2 - http://www.tandfonline.com/doi/full/10.1080/10715760701286159 DB - PRIME DP - Unbound Medicine ER -