title: TNFAIP1 contributes to the neurotoxicity induced by Aβ25-35 in Neuro2a cells.
abstract: 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.
  
  
  
  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.
  
  
  
  These results suggested that TNFAIP1 contributes to Aβ25-35-induced neurotoxicity by attenuating Akt/CREB signaling pathway, and Bcl-2 expression.
authors.affiliation: College of Medicine, Hunan Normal University, Changsha, China.|Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.|Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Neuroscience Program, Harvard Medical School, Boston, MA, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Neuroscience Program, Harvard Medical School, Boston, MA, USA.
authors.forename: Zhanyang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xun
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
authors.forename: Miaomiao
authors.initials: M
authors.lastname: Li
authors.affiliation: College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Peng
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pathology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
authors.forename: Manjun
authors.initials: M
authors.lastname: Yang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081, China.
authors.forename: Shiquan
authors.initials: S
authors.lastname: Gan
authors.affiliation: College of Medicine, Hunan Normal University, Changsha, China.
authors.forename: Shishan
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Neuroprotection Research Laboratory, Department of Neurology and Radiology, Massachusetts General Hospital, Neuroscience Program, Harvard Medical School, Boston, MA, USA.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081, China. xshlin@hunnu.edu.cn.
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Sciences, Hunan Normal University, Changsha, 410081, China. zhangjian@hunnu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005260:Female; D055785:Gene Knockdown Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity*; D010766:Phosphorylation / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016229:Amyloid beta-Peptides; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C485474:Tnfaip1 protein, mouse; C074636:amyloid beta-protein (25-35); C052617:Bcl2 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Alzheimer’s disease; Amyloid-beta; Neuro2a cells; Neurotoxicity; TNFAIP1