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Rockefeller, Weill Cornell researchers find link between estrogen, brain structure changes

D-95 protein translation. These switches involves rapid activation of an enzyme called Akt, a common intermediate in signaling pathways, which subsequently disinhibits 4E-BP1 (eukaryotic initiation factor-4E binding protein 1) to allow new protein synthesis.

"PSD-95 mRNA is hanging out near the spines and was not being translated because it had a big, inhibiting protein complex bound to it," says Akama. "Phosphorylation of 4E-BP1 disrupts this binding and when estrogen stimulates this release of 4E-BP1, new PSD-95 proteins were rapidly synthesized. More PSD-95 protein translated immediately at the spine increases spine maturation and synaptic formation. All this action is occurring far away from the nucleus, way off in the dendrite, without estrogen traveling back and forth down to the nucleus.

"In addition to the genomic mechanisms initiated within the nucleus, we have shown another way that estrogen can regulate dendritic function, and this gives us hope that selective agents can be developed that work through these signal pathways."


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Contact: Joseph Bonner
bonnerj@mail.rockefeller.edu
212-327-8998
Rockefeller University
14-Mar-2003


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