We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
TNFAIP1 contributes to the neurotoxicity induced by Aβ25-35 in Neuro2a cells.
- Authors
Ning Liu; Zhanyang Yu; Yu Xun; Miaomiao Li; Xiaoning Peng; Ye Xiao; Xiang Hu; Yi Sun; Manjun Yang; Shiquan Gan; Shishan Yuan; Xiaoying Wang; Shuanglin Xiang; Jian Zhang; Liu, Ning; Yu, Zhanyang; Xun, Yu; Li, Miaomiao; Peng, Xiaoning; Xiao, Ye
- Abstract
<bold>Background: </bold>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.<bold>Results: </bold>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.<bold>Conclusion: </bold>These results suggested that TNFAIP1 contributes to Aβ25-35-induced neurotoxicity by attenuating Akt/CREB signaling pathway, and Bcl-2 expression.
- Subjects
AMYLOID beta-protein; ALZHEIMER'S disease; NEUROTOXICOLOGY; APOPTOSIS; TUMOR necrosis factors; PROTEIN metabolism; RNA metabolism; ANIMAL experimentation; CELL lines; CELL physiology; CELLULAR signal transduction; CEREBRAL cortex; GENETIC techniques; MICE; NEURONS; PEPTIDES; PHOSPHORYLATION; POLYMERASE chain reaction; PROTEINS; TRANSFERASES; WESTERN immunoblotting
- Publication
BMC Neuroscience, 2016, Vol 17, p1
- ISSN
1471-2202
- Publication type
journal article
- DOI
10.1186/s12868-016-0286-3