C. Dominique Toran-Allerand, MD, ScD (hc)
Professor of Pathology & Cell Biology and Neurology
American Board of Psychiatry and Neurology (Neurology)
Tel: (212) 305-3620 (5-3620) || Fax: (212) 305-2134
Research Interests: Estrogen and the development of the brain and neural precursor cells.
» Recent Publications
Dr. Toran-Allerand has pioneered the study of estrogen action in the brain, when she was the first to document estrogen enhancement of neuronal growth and differentiation. She created the field of estrogen/neurotrophin interactions, after showing that estrogen receptors (ERs) co-localize extensively with the neurotrophins and their receptors in the brain and that basal forebrain cholinergic neurons, which are affected early in Alzheimer's disease, co-express estrogen and neurotrophin receptors These investigations lead to the novel hypothesis that estrogen and the neurotrophins influence each other's actions (1) by regulating receptor availability through reciprocal regulation at the transcriptional level and (2) through convergence of estrogen and neurotrophin signaling pathways, particularly at the level of the MAPK cascade In this first paper she and her colleagues documented the ability of estrogen to elicit rapid and sustained activation of the MAPK cascade, a pathway usually associated with the actions of growth factors such as the neurotrophins. The second paper proposed that the ER responsible for mediating estrogen activation of the MAPK cascade is neither the classical receptor ERalpha nor ERbeta. Her recent work on the intersection between estrogen action and neurotrophin signaling challenges conventional mainstream thinking and led to the hypothesis that this non-ERalpha/non-ERbeta receptor is associated with caveolar-like microdomains of the plasma membrane .These findings led directly to the identification of a novel putative membrane ER she has designated ER-X. This paper provides compelling evidence that ER-X is a novel and unique, plasma membrane-associated, developmentally regulated estrogen-binding protein which is functionally distinct from the classical intranuclear receptors ERalpha and ERbeta and is re-expressed following postnatal and adult ischemic brain injury. Current studies focus on the roles and mechanisms of 17alpha- and 17beta-estradiol action in cultures of the postnatal neocortex and in neural precursor cells of the adult rat hippocampal dentate gyrus and the therapeutic value of 17alpha-estradiol, the preferred ligand of ER-X.