RT Journal Article
SR Electronic
T1 Tumor Necrosis Factor Death Receptor Signaling Cascade Is Required for Amyloid-β Protein-Induced Neuron Death
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 1760
OP 1771
DO 10.1523/JNEUROSCI.4580-03.2004
VO 24
IS 7
A1 Rena Li
A1 Libang Yang
A1 Kristina Lindholm
A1 Yoshihiro Konishi
A1 Xu Yue
A1 Harald Hampel
A1 Dai Zhang
A1 Yong Shen
YR 2004
UL http://www.jneurosci.org/content/24/7/1760.abstract
AB 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-β protein (Aβ), 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 κB (NF-κB). Aβ-induced neuronal apoptosis was reduced with lower Apaf-1 expression, and little NF-κB 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 Aβ, which occurs through a TNF receptor signaling cascade and a caspase-dependent death pathway.