To further mechanistically explore the association between PGC-1α and BACE1, we overexpressed PGC-1α in cortical-hippocampal neuron cultures derived from Tg2576 mice. We found that the BACE1 levels were decreased by the PGC-1α expression, and this decrease was abolished by the PGC-1α gene silencing assessed by Western blot analysis (Fig. 5A). Because the ubiquitin-proteasome system (UPS) has been reported to be linked with BACE1 degradation, we then treated the adenoviral PGC-1α-infected neurons with lactacystin (5 µM), a specific proteasome inhibitor, for 4 hours. Consistent with our previous report, lactacystin significantly inhibited BACE1 degradation, suggesting that PGC-1α might exert influence on BACE1 via UPS-mediated degradation (Fig. 5B).