March 11, 2011
Neuroprotection and the trafficking of estradiol receptors
Dr. Rey Dominguez
Former MBRS-RISE MS to PhD Fellow Postdoctoral Zilkha Neurogenetics Institute
Keck School of Medicine of USC Zilkha Neurogenetics Institute
Keck School of Medicine of USC, Los Angeles, CA 90089-2821
Estradiol (17?-estradiol) is a steroid hormone involved in sexual reproductive development and regulating numerous brain functions. To date, these actions of estradiol are mediated by estradiol receptors (ER) by a mechanism that is sill not completely understood despite extensive research. In particular, estradiol is protective against excitotoxicity and other forms of brain injury, a property of the hormone that couples the activation of a subpopulation of nuclear ER? localized to the cell surface to the rapid activation of the extracellular-signal regulated kinase (ERK) pathway. The mechanism linking estradiol-initiated membrane signaling to ERK activation and neuroprotection remains unclear, however, recent studies provide mounting evidence that active cell surface ER? rapidly stimulates the activation of the G protein-coupled receptor kinase (GRK) and ?-arrestin pathway, a signaling cascade that couples the ERK pathway to receptor desensitization and down-regulation. Investigating this novel estradiol-signaling pathway will help provide insight into how neuroprotection is controlled and help explain a new mechanism of estradiol action in the brain and body.