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Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death
Li, R1; Yang, LB1; Lindholm, K1; Konishi, Y1; Yue, X1; Hampel, H1; Zhang, D1; Shen, Y1
关键词Alzheimer Apoptosis Death Degeneration Neuron Receptor
刊名JOURNAL OF NEUROSCIENCE
2004-02-18
DOI10.1523/JNEUROSCI.4580-03.2004
24期:7页:1760-1771
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Neurosciences
研究领域[WOS]Neurosciences & Neurology
关键词[WOS]NF-KAPPA-B ; SPORADIC ALZHEIMERS-DISEASE ; HUMAN NEUROBLASTOMA-CELLS ; TRAUMATIC BRAIN-INJURY ; A-BETA ; PRECURSOR PROTEIN ; NUCLEAR TRANSLOCATION ; ENDOPLASMIC-RETICULUM ; DEPENDENT ACTIVATION ; CALCIUM HOMEOSTASIS
英文摘要

Tumor necrosis factor type I receptor (TNFRI), a death receptor, mediates apoptosis and plays a crucial role in the interaction between the nervous and immune systems. A direct link between death receptor activation and signal cascade-mediated neuron death in brains with neurodegenerative disorders remains inconclusive. Here, we show that amyloid-beta protein (Abeta), a major component of plaques in the Alzheimer′s diseased brain, induces neuronal apoptosis through TNFRI by using primary neurons overexpressing TNFRI by viral infection or neurons from TNFRI knock-out mice. This was mediated via alteration of apoptotic protease-activating factor (Apaf-1) expression that in turn induced activation of nuclear factor kappaB (NF-kappaB). Abeta-induced neuronal apoptosis was reduced with lower Apaf-1 expression, and little NF-kappaB activation was found in the neurons with mutated Apaf-1 or a deletion of TNFRI compared with the cells from wild-type (WT) mice. Our studies suggest a novel neuronal response of Abeta, which occurs through a TNF receptor signaling cascade and a caspase-dependent death pathway.

语种英语
WOS记录号WOS:000189035300028
Citation statistics
Cited Times:110[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/50525
Collection北京大学精神卫生研究所
作者单位1.Sun Hlth Res Inst, Haldeman Lab Mol & Cellular Neurobiol, Sun City, AZ 85351 USA
2.Sun Hlth Res Inst, LJ Roberts Ctr Alzheimers Res, Alzheimers Res Lab, Sun City, AZ 85351 USA
3.Univ Munich, Dept Psychiat, D-80336 Munich, Germany
4.Beijing Univ, Sch Med, Inst Mental Hlth, Beijing 100871, Peoples R China
5.Arizona State Univ, Mol & Cellular Biol Program, Tempe, AZ 85287 USA
Recommended Citation
GB/T 7714
Li, R,Yang, LB,Lindholm, K,et al. Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death[J]. JOURNAL OF NEUROSCIENCE,2004,24(7):1760-1771.
APA Li, R.,Yang, LB.,Lindholm, K.,Konishi, Y.,Yue, X.,...&Shen, Y.(2004).Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death.JOURNAL OF NEUROSCIENCE,24(7),1760-1771.
MLA Li, R,et al."Tumor necrosis factor death receptor signaling cascade is required for amyloid-beta protein-induced neuron death".JOURNAL OF NEUROSCIENCE 24.7(2004):1760-1771.
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