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DYSREGULATION OF THE (IMMUNO)PROTEASOME PATHWAY IN MCD
differ from FCDs and was even longer compared to TSC cases. However, a positive cor- relation was observed between nuclear glial and neuronal proteasome subunit expres- sion and the pre-operative seizure frequency. We acknowledge limitations to the inter- pretation of these results, therefore an evaluation of the real biological contribution of proteasome subunit expression to seizure generation and frequency deserves further investigation in experimental models.
Several proteasome subunits show nuclear localization signaling 37 and previous studies in the human brain indicate that proteasomes are expressed in both cytoplasm and nuclei of different cell types, including glial and neuronal cells 24, 38. Immunoproteasome expression restricted to nuclei of astrocytes has been reported in the brain after an infection with lymphocytic choriomeningitis virus, suggesting involvement of the nuclear envelope in the compartmentalization of immature proteasome precursors 39. Whether the nuclear proteasome subunits represent (as suggested by Kremer et al., 39) immature proteasome precursors, or are proteolytically active remains still to be investigated. The nuclear proteasome subunit accumulation may reflect the induction of the proteasome system under conditions associated with cell injury and inflammation with possibility of nucleo-cytoplasmic transfer in cells, as glial cells, undergoing cell division or during apop-
Figure 7 Effects of rapamycin on proteasome subunit expression in astrocytes derived from FCD type II. Quantitative real-time PCR of proteasome expression in human FCD cells after 48 hours treatment with 100 nM rapamycin, under basal and stimulated (IL-1β 10 ng/ml) conditions. A and B: treatment with rapamycin decreased the expression of β1 (A) and β1i (B) subunit, both in basal and under stimulated conditions. C and D: treatment with rapamycin decreased the expression of β5 (C) and β5i (D) subunit under stimulated, but not in basal conditions. Data are expressed relative to the levels observed in untreated cells and are mean ± SEM (n=5). *p < 0.05, **p < 0.01 compared to control, Mann Whitney U test.
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