Immunocytochemical Localization of the 26S Proteasome Complex in Neurodegenerative Disorders and Controls

Background: A functional ubiquitin proteasome system (UPS) is essential for all eukaryotic cells and therefore any alteration to its components has potential pathological consequences. Aging and neurodegeneration are often accompanied by a functionally impaired ubiquitinproteasome system (UPS). The UPS orquestrates the turnover of innumerable proteins. Deregulation of the UPS has been implicated in the pathogenesis of many human diseases, cancer and neurodegenerative disorders. Methods: Immunocytochemistry with Peroxydase-anti-Peroxydase. We usedpostmortem material coming from patients suffering of tauo-and synucleinopathies. Young and old controls were included in all the experiments. Results: In the present study we tested a series of 59 antibodies. These were raised against different parts of the 26S proteasome complex.17 antibodies against the beta-subunitsand show cytoplasmic localisation.12 antibodies against the alpha subunits. They gave nuclear staining.20 antibodies against 19S regulator ATPase-dependent subunits and 7 antibodies against 19S regulator non-ATPase-dependent subunits. Only 2 subunits show strong immunoreactivity. From the 11S regulator 3 antibodies were used. We didnt find siginificant results from these antibodies. Young controlsshow no immunoreactivity, but old controls show some staining. Conclusions: Only some subunits have shown net differences with controls. These are the ATPase subunit S6b, the 20S 5, 6 and the 20S 6 subunits. As we see different cellular localization have been found in our investigations.