TNFAIP1 contributes to the neurotoxicity induced by Aβ25–35 in Neuro2a cells. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Liu, Ning; Yu, Zhanyang; Xun, Yu; Li, Miaomiao; Peng, Xiaoning; Xiao, Ye; Hu, Xiang; Sun, Yi; Yang, Manjun; Gan, Shiquan; Yuan, Shishan; Wang, Xiaoying; Xiang, Shuanglin; Zhang, Jian
• Is Part Of: BMC neuroscience. Volume 17:Issue 1(2016)
• Page Start: 1
• Page End: 10
• Publication Date: 2016-12
• Subjects: TNFAIP1 -- Amyloid-beta -- Alzheimer's disease -- Neurotoxicity -- Neuro2a cells; Neurosciences -- Periodicals; 573.805
• DOI: 10.1186/s12868-016-0286-3
• Languages: English
• ISSNs: 1471-2202

Abstract

Abstract 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 transgenicC. 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 Aβ25–35 . Knockdown and overexpression of TNFAIP1 significantly attenuated and exacerbated Aβ25–35 -induced neurotoxicity in N2a cells, respectively. Further studies showed that TNFAIP1 knockdown significantly blocked Aβ25–35 -induced cleaved caspase 3, whereas TNFAIP1 overexpression enhanced Aβ25–35 -induced cleaved caspase 3, suggesting that TNFAIP1 plays an important role in Aβ25–35 -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 Aβ25–35 on the levels of p-CREB and Bcl-2, while TNFAIP1 knockdown reversed Aβ25–35 -induced attenuation in the levels of p-CREB and Bcl-2. Conclusion These results suggested that TNFAIP1 contributes to Aβ25–35 -induced neurotoxicity by attenuating Akt/CREB signaling pathway, and Bcl-2 expression.