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 Aβ 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 Aβ1-42 levels increased. In cultured neuronal cells, an extracellular treatment of Aβ markedly decreased the proteasome activity and extracellular treated Aβ peptides were found in the cytoplasmic compartment. These results suggest that the extracellular Aβ peptides enter the cell and inhibit the proteasome activity, which might play a role in the pathogenesis of AD.