title: Novel interactions of GRP78: UPR and estrogen responses in the brain.
abstract: Glucose-regulated protein 78 (GRP78; 78 kDa) belongs to a group of highly conserved heat shock proteins (Hsp) with important functions at the cellular level. The emerging interest for GRP78 relies on its different functions, both in normal and pathological circumstances. GRP78 regulates intracellular calcium, protein shaping, endoplasmic reticulum (ER) stress and cell survival by an immediate response to insults, and that its expression may also be regulated by estrogens. Although these roles are well explored, the mechanisms by which GRP78 induces these changes are not completely understood. In this review, we highlight various aspects related to the GRP78 functioning in cellular protection and repair in response to ER stress and unfolded protein response by the regulation of intracellular Ca(2+) and other mechanisms. In this respect, the novel interactions between GRP78 and estrogens, such as estradiol and others, are analyzed in the context of the central nervous system (CNS). We also discuss the importance of GRP78 and estrogens in brain diseases including ischemia, Alzheimer's and Huntington's disorders. Finally, the main protective mechanisms of GRP78 and estrogens during ER dysfunction in the brain are described, and the prospective roles of GRP78 in therapeutic processes.
authors.affiliation: Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia.
authors.forename: Marco Fidel
authors.initials: MF
authors.lastname: Avila
authors.forename: Ricardo
authors.initials: R
authors.lastname: Cabezas
authors.forename: Daniel
authors.initials: D
authors.lastname: Torrente
authors.forename: Janneth
authors.initials: J
authors.lastname: Gonzalez
authors.forename: Ludis
authors.initials: L
authors.lastname: Morales
authors.forename: Lisandro
authors.initials: L
authors.lastname: Alvarez
authors.forename: Francisco
authors.initials: F
authors.lastname: Capani
authors.forename: George E
authors.initials: GE
authors.lastname: Barreto
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D004967:Estrogens / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D056811:Unfolded Protein Response / Q000502:physiology*
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D004967:Estrogens; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D002118:Calcium