Protective effect of 3H-1, 2-dithiole-3-thione on cellular model of Alzheimer's disease involves Nrf2/ARE signaling pathway

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator for a battery of genes encoding detoxifying and antioxidative enzymes. 3H-1, 2-dithiole-3-thione (D3T), a potent free radical scavenger, is able to activate Nrf2 signaling pathway. In the present study, N2a/APPswe cells were used as the Alzheimer's disease (AD) cellular model and we investigated the protective effect of D3T on N2a/APPswe cells and the potential mechanisms. Our assays demonstrated that D3T was able to attenuate reactive oxygen species generation, increase MMP level as well as decrease MDA content. Furthermore, treatment of the cells with 40 mu M D3T for 24 h, showed significant suppression of A beta level in N2a/APPswe cells. The current study also found that D3T significantly upregulated the Nrf2 mRNA level and protein expression, and subsequently enhanced mRNA expression of HO-1 and NQO1 in N2a/APPswe cells. Meanwhile, down-regulation of Nrf2 by small interference RNA abolished cytoprotection of D3T. Taken together, these results demonstrate that D3T provides neuroprotection in vitro model and therefore may be a potential complement for AD therapy.