A. Giovanni et al., Involvement of cell cycle elements, cyclin-dependent kinases, pRb, and E2Fcenter dot DP, in B-amyloid-induced neuronal death, J BIOL CHEM, 274(27), 1999, pp. 19011-19016
Previous evidence by others has indicated that a variety of cell cycle-rela
ted molecules are up-regulated in brains of Alzheimer's disease patients. T
he significance of this increase, however, is unclear. Accordingly, we exam
ined the obligate nature of cyclin-dependent kinases and select downstream
targets of these kinases in death of neurons evoked by B-amyloid (AB) prote
in. We present pharmacological and molecular biological evidence that cycli
n dependent kinases, in particular Cdk4/6, are required for such neuronal d
eath. 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.DP complex, is required for AB-evoked neuronal death. These results pro
vide evidence that cell cycle elements play a required role in death of neu
rons evoked by AB and suggest that these elements play an integral role in
Alzheimer's disease-related neuronal death.