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Seminars in Immunopathology
Published in: Seminars in Immunopathology 4/2015

01-07-2015 | Review

Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond

Authors: Amma F. Agyemang, Stephanie R. Harrison, Richard M. Siegel, Michael F. McDermott

Published in: Seminars in Immunopathology | Issue 4/2015

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Abstract

Cells have a number of mechanisms to maintain protein homeostasis, including proteasome-mediated degradation of ubiquitinated proteins and autophagy, a regulated process of “self-eating” where the contents of entire organelles can be recycled for other uses. The unfolded protein response prevents protein overload in the secretory pathway. In the past decade, it has become clear that these fundamental cellular processes also help contain inflammation though degrading pro-inflammatory protein complexes such as the NLRP3 inflammasome. Signaling pathways such as the UPR can also be co-opted by toll-like receptor and mitochondrial reactive oxygen species signaling to induce inflammatory responses. Mutations that alter key inflammatory proteins, such as NLRP3 or TNFR1, can overcome normal protein homeostasis mechanisms, resulting in autoinflammatory diseases. Conversely, Mendelian defects in the proteasome cause protein accumulation, which can trigger interferon-dependent autoinflammatory disease. In non-Mendelian inflammatory diseases, polymorphisms in genes affecting the UPR or autophagy pathways can contribute to disease, and in diseases not formerly considered inflammatory such as neurodegenerative conditions and type 2 diabetes, there is increasing evidence that cell intrinsic or environmental alterations in protein homeostasis may contribute to pathogenesis.
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Metadata
Title
Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond
Authors
Amma F. Agyemang
Stephanie R. Harrison
Richard M. Siegel
Michael F. McDermott
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Seminars in Immunopathology / Issue 4/2015
Print ISSN: 1863-2297
Electronic ISSN: 1863-2300
DOI
https://doi.org/10.1007/s00281-015-0496-2

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