Role of endoplasmic reticulum stress and protein misfolding in disorders of the liver and pancreas

Jan Lukas, Jola Pospech, Christina Oppermann, Christina Hund, Katharina Iwanov, Supansa Pantoom, Janine Petters, Moritz Frech, Susanne Seemann, Franziska Gisela Thiel, Jana Marielle Modenbach, Robert Bolsmann, Laura de Freitas Chama, Franziska Kraatz, Firas El-Hage, Manuel Gronbach, Annelie Klein, Regina Müller, Sabine Salloch, Frank Ulrich WeissPeter Simon, Preshit Wagh, Almuth Klemenz, Elke Krüger, Julia Mayerle, Mihaela Delcea, Udo Kragl, Matthias Beller, Arndt Rolfs, Markus M. Lerch, Matthias Sendler

Research output: Contribution to journalReview articlepeer-review

39 Scopus citations

Abstract

The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane and secretory proteins. The fraction of protein passing through the ER represents a large proportion of the total protein in the cell. Protein folding, glycosylation, sorting and transport are essential tasks of the ER and a compromised ER folding network has been recognized to be a key component in the disease pathogenicity of common neurodegenerative, metabolic and malignant diseases. On the other hand, the ER protein folding machinery also holds significant potential for therapeutic interventions. Many causes can lead to ER stress. A disturbed calcium homeostasis, the generation of reactive oxygen species (ROS) and a persistent overload of misfolded proteins within the ER can drive the course of adisease. In this review the role of ER-stress in diseases of the liver and pancreas will be examined using pancreatitis and Wilson´s disease as examples. Potential therapeutic targets in ER-stress pathways will also be discussed.

Original languageEnglish
Pages (from-to)315-323
Number of pages9
JournalAdvances in Medical Sciences
Volume64
Issue number2
DOIs
StatePublished - Sep 2019
Externally publishedYes

Keywords

  • ER stress
  • Endoplasmic reticulum associated protein degradation-ERAD
  • Pancreatitis
  • Unfolded protein response
  • Wilson's disease

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