Smith WW, Norton DD, Gorospe M, Jiang H, Nemoto S, Holbrook NJ, Finkel T, Kusiak JW.
Phosphorylation of p66Shc and forkhead proteins mediates Abeta toxicity.
J Cell Biol. 2005 Apr 25;169(2):331-9.
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This is an elegant paper demonstrating downstream events that tie Abeta toxicity and oxidative stress.
The results reported in this paper demonstrate that p66Shc is involved in the neuronal death induced in vitro by Aβ. Further studies on this topic could be of help to address the relevance of oxidative stress induced by Aβ in vivo, and its role in AD neurodegeneration. Thus, it is now important to examine the phosphorylation state of p66Shc in AD brains and in mouse models of AD, and to analyze the phenotype of these models in a background lacking p66Shc.