The proteasome in brain aging

The proteasome is a large intracellular protease, present in all cells of the central nervous system (CNS), that is responsible for the majority of intracellular protein degradation. In particular, the proteasome is responsible for the degradation of most oxidized, aggregated, and misfolded proteins. The importance of proteasome activity to neuronal homeostasis is highlighted by previous studies demonstrating that proteasome inhibition alone is sufficient to induce neuron death in vitro. Recent studies indicate that alterations in proteasome activity may occur during, and possibly contribute to, the aging process. These data raise the possibility that alterations in the proteasome proteolytic pathway may contribute to the elevations in protein oxidation, protein aggregation, and neurodegeneration evident in the aging CNS. The focus of this review is to describe what is currently known about the proteasome in the CNS, describe established age-related alterations in proteasome biology, and to discuss how such alterations in proteasome biology may ultimately contribute to the aging of the CNS.