Get access

Novel interactions of GRP78: UPR and estrogen responses in the brain

Authors

  • Marco Fidel Avila,

    1. Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia
    Search for more papers by this author
  • Ricardo Cabezas,

    1. Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia
    Search for more papers by this author
  • Daniel Torrente,

    1. Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia
    Search for more papers by this author
  • Janneth Gonzalez,

    1. Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia
    Search for more papers by this author
  • Ludis Morales,

    1. Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia
    Search for more papers by this author
  • Lisandro Alvarez,

    1. Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas Prof. Dr. Alberto C. Taquini (ININCA), Facultad de Medicina, UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ Buenos Aires, Argentina
    Search for more papers by this author
  • Francisco Capani,

    1. Laboratorio de Citoarquitectura y Plasticidad Neuronal, Instituto de Investigaciones Cardiológicas Prof. Dr. Alberto C. Taquini (ININCA), Facultad de Medicina, UBA-CONICET, Marcelo T. de Alvear 2270, C1122AAJ Buenos Aires, Argentina
    Search for more papers by this author
  • George E. Barreto

    Corresponding author
    • Departamento de Nutrición y Bioquímica, Facultad de Ciencias, Pontificia Universidad Javeriana, Bogotá D.C., Colombia
    Search for more papers by this author

Corresponding author: e-mail: gsampaio@javeriana.edu.co

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 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.

Get access to the full text of this article

Ancillary