The deposition of Aβ has long been implicated in the cellular damage and subsequent cognitive dysfunction of Alzheimer's disease, but the mechanism for this remains unclear. Recently, evidence has accumulated linking Aβ to neuronal apoptosis. In today's Journal of Neuroscience, researchers in Michael Greenberg's lab at Children's Hospital in Boston show that Aβ-induced neuronal death may be linked to the apoptotic factor Fas ligand (FasL).

The authors found that the fibrillar form of Aβ (Aβ25-35) caused apoptosis of cortical neurons in culture, which was accompanied by a twofold increase in Jun N-terminal kinase (JNK) activity and an increase in the phosphorylation of its substrate c-Jun; these observations are consistent with earlier data indicating that c-Jun is necessary for Aβ-induced neuronal cell death ( Kihiko et al 1999 ). In addition, Aβ-induced synthesis of FasL in neuronal culture, but neurons that were negative for JNK3 not only failed to activate as much c-Jun as did wildtype, but also failed to produce FasL.

The data suggests that amyloid-induced cell death is mediated by c-Jun, which in turn leads to activation of FasL and the apoptotic pathway. In support of this, cells carrying mutations in FasL, or its receptor Fas, were much less likely to undergo apoptosis when challenged with Aβ25-35. In addition, the researchers were able to show that inhibition of caspase 8, a downstream target of FasL/Fas, attenuates the effects of Aβ.-Tom Fagan.
References: Morishima Y, Gotoh Y, Zieg J, Barrett T, Takano H, Flavell R, Davis RJ, Shirasaki Y, Greenberg ME. b-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J Neurosci. 2001 Oct 1;21(19):7551-60. Abstract

Comments

Make a Comment

To make a comment you must login or register.

Comments on this content

No Available Comments

Comments on Primary Papers for this Article

No Available Comments on Primary Papers for this Article

References

Paper Citations

  1. . Beta-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J Neurosci. 2001 Oct 1;21(19):7551-60. PubMed.

External Citations

  1. Kihiko et al 1999

Further Reading

Papers

  1. . Beta-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J Neurosci. 2001 Oct 1;21(19):7551-60. PubMed.

Primary Papers

  1. . Beta-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand. J Neurosci. 2001 Oct 1;21(19):7551-60. PubMed.