TY - JOUR
T1 - Novel interactions of GRP78
T2 - UPR and estrogen responses in the brain
AU - Avila, Marco Fidel
AU - Cabezas, Ricardo
AU - Torrente, Daniel
AU - Gonzalez, Janneth
AU - Morales, Ludis
AU - Alvarez, Lisandro
AU - Capani, Francisco
AU - Barreto, George E.
N1 - © 2013 International Federation for Cell Biology.
PY - 2013/6
Y1 - 2013/6
N2 - 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 Ca2+ 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.
AB - 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 Ca2+ 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.
KW - Calcium
KW - Estrogens
KW - GRP78
KW - Neuroprotection
KW - Unfolded protein response
UR - http://www.scopus.com/inward/record.url?scp=84878167023&partnerID=8YFLogxK
U2 - 10.1002/cbin.10058
DO - 10.1002/cbin.10058
M3 - Article
C2 - 23494837
AN - SCOPUS:84878167023
SN - 1065-6995
VL - 37
SP - 521
EP - 532
JO - Cell Biology International
JF - Cell Biology International
IS - 6
ER -