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Sci. STKE, 9 October 2001
Vol. 2001, Issue 103, p. tw368
[DOI: 10.1126/stke.2001.103.tw368]


Apoptosis Amyloid β-Protein Promotes Apoptosis Through Jnk3 and Fas

The presence of amyloid β-protein (Aβ) deposits in brain plaques correlates with neural degeneration and cognitive loss in Alzheimer's disease patients, and it is widely thought that Aβ might mediate neuronal apoptosis. Now, Morishima et al. provide a mechanism whereby the presence of Aβ can lead to cell death. The authors observed that cultured neurons treated with Aβ underwent apotosis and that apoptosis was preceded by the activation of c-Jun NH2-terminal kinase (Jnk) and an increase in the transcriptional activation of c-Jun. Neurons from Jnk3-deficient mice exhibited reduced Aβ-dependent apoptosis, indicating that Jnk activity is required to mediate apoptosis in Aβ-treated neurons. Neurons treated with Aβ had increased amounts of Fas ligand, an effect that also required the activity of Jnk3. Caspase-8 activation and subsequent neuronal apoptosis was dependent on the association of Fas ligand with Fas. Thus, the authors have unraveled a pathway whereby Aβ induces the death of neuronal cells in culture, and suggest that the JNK pathway might have a role in Aβ-directed neuronal death in patients with Alzheimer's disease.

Y. Morishima, Y. Gotoh, J. Zieg, T. Barrett, H. Takano, R. Flavell, R. J. Davis, Y. Shirasaki, M. E. Greenberg, β-Amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J. Neurosci. 21, 7551-7560 (2001). [Abstract] [Full Text]

Citation: Amyloid β-Protein Promotes Apoptosis Through Jnk3 and Fas. Sci. STKE 2001, tw368 (2001).

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