Agyemang, A, Harrison, SR, Siegel, RM et al. (1 more author) (2015) Protein misfolding and dysregulated protein homeostasis in autoinflammatory diseases and beyond. Seminars in Immunopathology, 37 (4). pp. 335-347. ISSN 1863-2297
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015, Springer. This is an author produced version of a paper published in Seminars in Immunopathology. Uploaded in accordance with the publisher's self-archiving policy. The final publication is available at Springer via http://dx.doi.org/10.1007/s00281-015-0496-2. |
Keywords: | Protein misfolding; autoinflammatory; unfolded protein response; TRAPS |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Experimental Musculoskeletal Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 28 May 2015 12:34 |
Last Modified: | 23 May 2016 01:26 |
Published Version: | http://dx.doi.org/10.1007/s00281-015-0496-2 |
Status: | Published |
Publisher: | Springer |
Refereed: | Yes |
Identification Number: | 10.1007/s00281-015-0496-2 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:86335 |