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 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.
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| http://dx.doi.org/10.1186/s12868-016-0286-3 | DOI Listing |
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