Amyloid-β (Aβ) plays a critical role in the pathogenesis of Alzheimer's disease (AD), an age-related neurodegenerative ailment. Emerging evidence suggests that Tenuifolin (TEN) significantly decreases Aβ secretion and relieves cellular inflammatory responses. However, the mechanism of this activity has not been fully elucidated. In the present study, we investigate the effect of TEN on autophagy, a process that plays an important role in the generation and metabolism of Aβ, in the presence or absence of the autophagy inhibitor 3-MA. The obtained results show that TEN prevents Aβ25-35-induced inflammation and decreases Aβ1-40 and Aβ1-42 levels by decreasing BACE1 in SH-SY5Y cells. Moreover, TEN decreases the mRNA levels of BACE1 but has no impact on the gene expressions of amyloid precursor proteins (APP). 3-MA, the most widely used autophagy inhibitor, reverses the effects of TEN in Aβ25-35-induced SH-SY5Y cells. The association between TEN and autophagy was further investigated by examining the levels of autophagy markers LC3 II and Beclin 1, as well as the protein levels of mTOR, AMPK, and ULK1. The results showed that TEN increases LC3 II, Beclin 1, and mTOR, inhibits the degradation of AMPK, and increases the expression of ULK1. This suggests that TEN protects against Aβ25-35-induced cellular inflammation in an AD cell model through the regulation of autophagy, which, in part, is mediated by the activation of the AMPK/mTOR/ULK1 pathway.
Keywords: Alzheimer’s disease; Autophagy; BACE1; Inflammation; Tenuifolin.
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