Your browser doesn't support javascript.
loading
Small molecule strategies to harness the unfolded protein response: where do we go from here?
Grandjean, Julia M D; Wiseman, R Luke.
Afiliación
  • Grandjean JMD; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA.
  • Wiseman RL; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, California, USA. Electronic address: wiseman@scripps.edu.
J Biol Chem ; 295(46): 15692-15711, 2020 11 13.
Article en En | MEDLINE | ID: mdl-32887796
The unfolded protein response (UPR) plays a central role in regulating endoplasmic reticulum (ER) and global cellular physiology in response to pathologic ER stress. The UPR is comprised of three signaling pathways activated downstream of the ER membrane proteins IRE1, ATF6, and PERK. Once activated, these proteins initiate transcriptional and translational signaling that functions to alleviate ER stress, adapt cellular physiology, and dictate cell fate. Imbalances in UPR signaling are implicated in the pathogenesis of numerous, etiologically-diverse diseases, including many neurodegenerative diseases, protein misfolding diseases, diabetes, ischemic disorders, and cancer. This has led to significant interest in establishing pharmacologic strategies to selectively modulate IRE1, ATF6, or PERK signaling to both ameliorate pathologic imbalances in UPR signaling implicated in these different diseases and define the importance of the UPR in diverse cellular and organismal contexts. Recently, there has been significant progress in the identification and characterization of UPR modulating compounds, providing new opportunities to probe the pathologic and potentially therapeutic implications of UPR signaling in human disease. Here, we describe currently available UPR modulating compounds, specifically highlighting the strategies used for their discovery and specific advantages and disadvantages in their application for probing UPR function. Furthermore, we discuss lessons learned from the application of these compounds in cellular and in vivo models to identify favorable compound properties that can help drive the further translational development of selective UPR modulators for human disease.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Bibliotecas de Moléculas Pequeñas / Respuesta de Proteína Desplegada Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Bibliotecas de Moléculas Pequeñas / Respuesta de Proteína Desplegada Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: J Biol Chem Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos