TNFAIP1 contributes to the neurotoxicity induced by Aβ(25–35) in Neuro2a cells

BACKGROUND: Amyloid-beta (Aβ) accumulation is a hallmark of Alzheimer’s disease (AD) that can lead to neuronal dysfunction and apoptosis. Tumor necrosis factor, alpha-induced protein 1 (TNFAIP1) is an apoptotic protein that was robustly induced in the transgenic C. elegans AD brains. However, the roles of TNFAIP1 in AD have not been investigated. RESULTS: We found TNFAIP1 protein and mRNA levels were dramatically elevated in primary mouse cortical neurons and Neuro2a (N2a) cells exposed to Aβ(25–35). Knockdown and overexpression of TNFAIP1 significantly attenuated and exacerbated Aβ(25–35)-induced neurotoxicity in N2a cells, respectively. Further studies showed that TNFAIP1 knockdown significantly blocked Aβ(25–35)-induced cleaved caspase 3, whereas TNFAIP1 overexpression enhanced Aβ(25–35)-induced cleaved caspase 3, suggesting that TNFAIP1 plays an important role in Aβ(25–35)-induced neuronal apoptosis. Moreover, we observed that TNFAIP1 was capable of inhibiting the levels of phosphorylated Akt and CREB, and also anti-apoptotic protein Bcl-2. TNFAIP1 overexpression enhanced the inhibitory effect of Aβ(25–35) on the levels of p-CREB and Bcl-2, while TNFAIP1 knockdown reversed Aβ(25–35)-induced attenuation in the levels of p-CREB and Bcl-2. CONCLUSION: These results suggested that TNFAIP1 contributes to Aβ(25–35)-induced neurotoxicity by attenuating Akt/CREB signaling pathway, and Bcl-2 expression.