title: Neuroprotective effects of non-classical estrogen-like signaling activators: from mechanism to potential implications.
abstract: The gonadal steroid 17β-estradiol (E2) has shown powerful cytoprotective effect on cells. In addition to classical genomic mechanisms of action, E2 also exerts non-classical effects on intracellular signal transduction. Extensive studies during the past two decades have provided evidence that the E2-induced non-classical signaling on second messenger molecules plays a critical role in the neuroprotective effect of E2. These observations provide a unique basis for developing non-classical estrogen-like signaling activators that may have potential for clinical use in neuroprotection. In spite of the extensive research over the past decade reviewed here, we are just starting to appreciate the importance and potential of these compounds. Hence, we first describe the molecular characteristics and effects of these activators. Second, we survey recent data as to possible mechanisms underlying the ameliorative actions of selective non-classical estrogen-like signaling activation. In addition, the pitfalls and future aspects of "non-classical"-line activators and its clinical relevance will also be discussed.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kwakowsky
authors.forename: Zsombor
authors.initials: Z
authors.lastname: Koszegi
authors.forename: Rachel Y
authors.initials: RY
authors.lastname: Cheong
authors.affiliation: Centre for Neuroendocrinology & Department of Physiology, University of Otago, Lindo Ferguson Building, 270 Great King Street, PO Box 913, 9054, Dunedin, New Zealand. istvan.abraham@otago.ac.nz.
authors.forename: István M
authors.initials: IM
authors.lastname: Abrahám
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D004958:Estradiol / Q000008:administration & dosage; D004967:Estrogens / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D004967:Estrogens; D018696:Neuroprotective Agents; D004958:Estradiol