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J Biol Chem. 1999 Jul 2;274(27):19011-6.

Involvement of cell cycle elements, cyclin-dependent kinases, pRb, and E2F x DP, in B-amyloid-induced neuronal death.

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Hoechst Marion Roussel, Neuroscience, Bridgewater, New Jersey 08807, USA.


Previous evidence by others has indicated that a variety of cell cycle-related molecules are up-regulated in brains of Alzheimer's disease patients. The significance of this increase, however, is unclear. Accordingly, we examined the obligate nature of cyclin-dependent kinases and select downstream targets of these kinases in death of neurons evoked by B-amyloid (AB) protein. We present pharmacological and molecular biological evidence that cyclin-dependent kinases, in particular Cdk4/6, are required for such neuronal death. In addition, we demonstrate that the substrate of Cdk4/6, pRb/p107, is phosphorylated during AB treatment and that one target of pRb/p107, the E2F x DP complex, is required for AB-evoked neuronal death. These results provide evidence that cell cycle elements play a required role in death of neurons evoked by AB and suggest that these elements play an integral role in Alzheimer's disease-related neuronal death.

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