NR reduces BACE1 levels through promotion of PGC-1α expression

Because NR treatment reducing Aβ levels is coincident with the enhanced expression of PGC-1α, which has been associated with degradation of BACE1 (Gong et al., 2010), next we tested if the effects of NR on the Aβ levels is also via a regulation on BACE1 degradation.
We tested the protein levels of BACE1 and PGC-1α in primary cultured cortical neurons from brains of Tg2576 mice treated with NR. We first confirmed the effects of NR on the promotion of PGC-1α expression by Western blot analysis, though this increase was abolished by the infection of adenoviral PGC-1α shRNA (Fig. 4A). Next, we probed the levels of BACE1 protein and found that BACE1 protein levels were significantly decreased by NR treatment, and this decrease was largely abolished by PGC-1α silencing by adenoviral PGC-1α shRNA (Fig. 4B), suggesting that NR affects the Aβ levels through regulation of PGC-1α expression.