LAUSR

Defects in the activity of the proteasome or its regulators are linked to several pathologies, including neurodegenerative diseases. We hypothesize that proteasome heterogeneity and its selective partners vary across brain regions and have a significant impact on proteasomal catalytic activities. Using neuronal cell cultures and brain tissues obtained from mice, we compared proteasomal activities from two distinct brain regions affected in neurodegenerative diseases, the striatum and the hippocampus. The results indicated that proteasome activities and their responses to proteasome inhibitors are determined by their subcellular localizations and their brain regions. Using an iodixanol gradient fractionation method, proteasome complexes were isolated, followed by proteomic analysis for proteasomal interaction partners. Proteomic results revealed brain region-specific non-proteasomal partners, including gamma-enolase (ENO2). ENO2 showed more association to proteasome complexes purified from the striatum than to those from the hippocampus. These results highlight a potential key role for non-proteasomal partners of proteasomes regarding the diverse activities of the proteasome complex recorded in several brain regions.