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Inflamm Bowel Dis. 2018 Dec 24. doi: 10.1093/ibd/izy380. [Epub ahead of print]

Interactions Between Autophagy and the Unfolded Protein Response: Implications for Inflammatory Bowel Disease.

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School of Applied Sciences, Edinburgh Napier University, Edinburgh, United Kingdom.
Child Life and Health, University of Edinburgh, Edinburgh, United Kingdom.
Department of Paediatric Gastroenterology and Nutrition, Royal Hospital for Sick Children, Edinburgh, United Kingdom.


Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis, is characterized by chronic inflammation of the gastrointestinal tract. The etiology involves a combination of genetic and environmental factors resulting in abnormal immune responses to intestinal microbiota. Genetic studies have strongly linked genes involved in autophagy to CD, and genes involved in the unfolded protein response (UPR) to IBD. The UPR is triggered in response to accumulation of misfolded proteins in the endoplasmic reticulum (ER), and autophagy plays a key role in relieving ER stress and restoring homeostasis. This review summarizes the known interactions between autophagy and the UPR and discusses the impact of these converging pathways on IBD pathogenesis. With a paucity of effective long-term treatments for IBD, targeting of synergistic pathways may provide novel and more effective therapeutic options.


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