Amyloid peptide attenuates the proteasome activity in neuronal cells

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.