Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases
Proteostasis, a portmanteau of the words protein and homeostasis, refers to the ability of eukaryotic cells to maintain a stable proteome by acting on protein synthesis, quality control and/or degradation. Over the last two decades, an increasing number of disorders caused by proteostasis perturbati...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/9/1422 |
| _version_ | 1797505315357327360 |
|---|---|
| author | Jonas Johannes Papendorf Elke Krüger Frédéric Ebstein |
| author_facet | Jonas Johannes Papendorf Elke Krüger Frédéric Ebstein |
| author_sort | Jonas Johannes Papendorf |
| collection | DOAJ |
| description | Proteostasis, a portmanteau of the words protein and homeostasis, refers to the ability of eukaryotic cells to maintain a stable proteome by acting on protein synthesis, quality control and/or degradation. Over the last two decades, an increasing number of disorders caused by proteostasis perturbations have been identified. Depending on their molecular etiology, such diseases may be classified into ribosomopathies, proteinopathies and proteasomopathies. Strikingly, most—if not all—of these syndromes exhibit an autoinflammatory component, implying a direct cause-and-effect relationship between proteostasis disruption and the initiation of innate immune responses. In this review, we provide a comprehensive overview of the molecular pathogenesis of these disorders and summarize current knowledge of the various mechanisms by which impaired proteostasis promotes autoinflammation. We particularly focus our discussion on the notion of how cells sense and integrate proteostasis perturbations as danger signals in the context of autoinflammatory diseases to provide insights into the complex and multiple facets of sterile inflammation. |
| first_indexed | 2024-03-10T04:16:51Z |
| format | Article |
| id | doaj.art-4cee4c6fa55842df8d2185120990896d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T04:16:51Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-4cee4c6fa55842df8d2185120990896d2023-11-23T07:59:02ZengMDPI AGCells2073-44092022-04-01119142210.3390/cells11091422Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory DiseasesJonas Johannes Papendorf0Elke Krüger1Frédéric Ebstein2Institut für Medizinische Biochemie und Molekularbiologie, Universitätsmedizin Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyInstitut für Medizinische Biochemie und Molekularbiologie, Universitätsmedizin Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyInstitut für Medizinische Biochemie und Molekularbiologie, Universitätsmedizin Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyProteostasis, a portmanteau of the words protein and homeostasis, refers to the ability of eukaryotic cells to maintain a stable proteome by acting on protein synthesis, quality control and/or degradation. Over the last two decades, an increasing number of disorders caused by proteostasis perturbations have been identified. Depending on their molecular etiology, such diseases may be classified into ribosomopathies, proteinopathies and proteasomopathies. Strikingly, most—if not all—of these syndromes exhibit an autoinflammatory component, implying a direct cause-and-effect relationship between proteostasis disruption and the initiation of innate immune responses. In this review, we provide a comprehensive overview of the molecular pathogenesis of these disorders and summarize current knowledge of the various mechanisms by which impaired proteostasis promotes autoinflammation. We particularly focus our discussion on the notion of how cells sense and integrate proteostasis perturbations as danger signals in the context of autoinflammatory diseases to provide insights into the complex and multiple facets of sterile inflammation.https://www.mdpi.com/2073-4409/11/9/1422proteostasisautoinflammationribosomopathiesproteinopathiesproteasomopathies |
| spellingShingle | Jonas Johannes Papendorf Elke Krüger Frédéric Ebstein Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases Cells proteostasis autoinflammation ribosomopathies proteinopathies proteasomopathies |
| title | Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases |
| title_full | Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases |
| title_fullStr | Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases |
| title_full_unstemmed | Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases |
| title_short | Proteostasis Perturbations and Their Roles in Causing Sterile Inflammation and Autoinflammatory Diseases |
| title_sort | proteostasis perturbations and their roles in causing sterile inflammation and autoinflammatory diseases |
| topic | proteostasis autoinflammation ribosomopathies proteinopathies proteasomopathies |
| url | https://www.mdpi.com/2073-4409/11/9/1422 |
| work_keys_str_mv | AT jonasjohannespapendorf proteostasisperturbationsandtheirrolesincausingsterileinflammationandautoinflammatorydiseases AT elkekruger proteostasisperturbationsandtheirrolesincausingsterileinflammationandautoinflammatorydiseases AT fredericebstein proteostasisperturbationsandtheirrolesincausingsterileinflammationandautoinflammatorydiseases |