Journal
MECHANISMS OF AGEING AND DEVELOPMENT
Volume 126, Issue 12, Pages 1292-1299Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2005.07.006
Keywords
Tg2576; proteasome; chymotrypsin-like activity; amyloid beta-peptide
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Previous studies have suggested a possible relationship between the ubiquitin-proteasome pathway and some pathological manifestations of Alzheimer's disease (AD). This study investigated the possibility that the A beta peptides interact with the ubiquitin-proteasome pathway inside neuronal cells. The ubiquitin-proteasome activity decreased with age in the brains of Tg2576 mice while the A beta(1-42) levels increased. In cultured neuronal cells, an extracellular treatment of A beta markedly decreased the proteasome activity and extracellular treated A beta peptides were found in the cytoplasmic compartment. These results suggest that the extracellular A beta peptides enter the cell and inhibit the proteasome activity, which might play a role in the pathogenesis of AD. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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