The proteasome system and proteasome inhibitors in stroke: controlling the inflammatory response

The ubiquitin-proteasome pathway (UPP) is a predominantly non-lysosomal protein degradation pathway responsible for degrading many critical regulatory proteins (e.g., nuclear factor-kappa B). This pathway is widely known for its ubiquitous role in immune and inflammatory responses, control of cell growth and apoptosis. These roles are apparent in the nervous system, but neurons and their neighboring cells also employ the UPP for distinct functions, ranging from development to the co-ordination of cellular responses, injury of the nervous system and brain-specific processes such as aging and memory. Promising results from preclinical studies in animal models indicate that the use of specific proteasome inhibitors to manipulate UPP may prove valuable in treating such conditions as ischemic stroke.