Islet stress, degradation and autoimmunity

Diabetes, Obesity & Metabolism
Sofia ThomaidouBart O Roep

Abstract

β-cell destruction in type 1 diabetes (T1D) results from the effect of inflammation and autoimmunity. In response to inflammatory signals, islet cells engage adaptive mechanisms to restore and maintain cellular homeostasis. Among these mechanisms, the unfolded protein response (UPR) leads to a reduction of the general protein translation rate, increased production of endoplasmic reticulum chaperones and the initiation of degradation by activation of the ER associated degradation pathway (ERAD) in which newly synthetized proteins are ubiquitinylated and processed through the proteasome. This adaptive phase is also believed to play a critical role in the development of autoimmunity by the generation of neoantigens. While we have previously investigated the effect of stress on transcription, translation and post-translational events as possible source for neoantigens, the participation of the degradation machinery, yet crucial in the generation of antigenic peptides, remains to be investigated in the context of T1D pathology. In this review, we will describe the relation between the unfolded protein response and the Ubiquitin Proteasome System (UPS) and address the role of the cellular degradation machinery in the generation of an...Continue Reading

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Citations

Jun 7, 2019·Diabetes Care·Maria J RedondoJay Sosenko
Aug 28, 2019·Diabetologia·Maria E CraigWilliam D Rawlinson
May 14, 2020·Nature Reviews. Endocrinology·Décio L EizirikMiriam Cnop
May 13, 2020·PPAR Research·Laurits J HolmKarsten Buschard
May 6, 2020·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·Mengwei LiuWanyang Liu
Dec 10, 2020·Nature Reviews. Endocrinology·Bart O RoepArnaud Zaldumbide
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May 4, 2021·Frontiers in Immunology·Saurabh VigBruno Guigas

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Methods Mentioned

BETA
deamidation

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