Proteostasis signatures in human diseases.
The protein homeostasis (proteostasis) network maintains the proteome in a functional state. Although this network has been comprehensively mapped, its perturbations in disease remain incompletely characterised. To address this problem, here we define the proteostasis signatures, which represent the...
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2025-06-01
|
| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1013155 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849686740372029440 |
|---|---|
| author | Christine M Lim Michele Vendruscolo |
| author_facet | Christine M Lim Michele Vendruscolo |
| author_sort | Christine M Lim |
| collection | DOAJ |
| description | The protein homeostasis (proteostasis) network maintains the proteome in a functional state. Although this network has been comprehensively mapped, its perturbations in disease remain incompletely characterised. To address this problem, here we define the proteostasis signatures, which represent the characteristic patterns of change in the proteostasis network associated with disease. We performed a large-scale, pan-disease analysis across 32 human diseases spanning 7 disease types. We first identified unique proteostasis perturbations in specific disease states. We then uncovered distinctive signatures differentiating disease types, pointing to a range of proteostasis mechanisms in disease development. Next, we tracked the temporal evolution of proteostasis signatures, revealing shifts in proteostasis disruption over the course of disease progression. Finally, we demonstrated how smoking, a major risk factor for many diseases, impairs proteostasis in a manner similar to disease, potentially creating a predisposed environment for disease onset. These results illustrate the opportunities offered by the study of human diseases from the perspective of proteostasis signatures. |
| format | Article |
| id | doaj-art-a4931ee3a97d44e68288020015a6bbb9 |
| institution | DOAJ |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-a4931ee3a97d44e68288020015a6bbb92025-08-20T03:22:35ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-06-01216e101315510.1371/journal.pcbi.1013155Proteostasis signatures in human diseases.Christine M LimMichele VendruscoloThe protein homeostasis (proteostasis) network maintains the proteome in a functional state. Although this network has been comprehensively mapped, its perturbations in disease remain incompletely characterised. To address this problem, here we define the proteostasis signatures, which represent the characteristic patterns of change in the proteostasis network associated with disease. We performed a large-scale, pan-disease analysis across 32 human diseases spanning 7 disease types. We first identified unique proteostasis perturbations in specific disease states. We then uncovered distinctive signatures differentiating disease types, pointing to a range of proteostasis mechanisms in disease development. Next, we tracked the temporal evolution of proteostasis signatures, revealing shifts in proteostasis disruption over the course of disease progression. Finally, we demonstrated how smoking, a major risk factor for many diseases, impairs proteostasis in a manner similar to disease, potentially creating a predisposed environment for disease onset. These results illustrate the opportunities offered by the study of human diseases from the perspective of proteostasis signatures.https://doi.org/10.1371/journal.pcbi.1013155 |
| spellingShingle | Christine M Lim Michele Vendruscolo Proteostasis signatures in human diseases. PLoS Computational Biology |
| title | Proteostasis signatures in human diseases. |
| title_full | Proteostasis signatures in human diseases. |
| title_fullStr | Proteostasis signatures in human diseases. |
| title_full_unstemmed | Proteostasis signatures in human diseases. |
| title_short | Proteostasis signatures in human diseases. |
| title_sort | proteostasis signatures in human diseases |
| url | https://doi.org/10.1371/journal.pcbi.1013155 |
| work_keys_str_mv | AT christinemlim proteostasissignaturesinhumandiseases AT michelevendruscolo proteostasissignaturesinhumandiseases |