Genome instability and loss of protein homeostasis: converging paths to neurodegeneration?
Genome instability and loss of protein homeostasis are hallmark events of age-related diseases that include neurodegeneration. Several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis are characterized...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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The Royal Society
2021-04-01
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| Series: | Open Biology |
| Subjects: | |
| Online Access: | https://royalsocietypublishing.org/doi/10.1098/rsob.200296 |
| _version_ | 1811190071023370240 |
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| author | Anna Ainslie Wouter Huiting Lara Barazzuol Steven Bergink |
| author_facet | Anna Ainslie Wouter Huiting Lara Barazzuol Steven Bergink |
| author_sort | Anna Ainslie |
| collection | DOAJ |
| description | Genome instability and loss of protein homeostasis are hallmark events of age-related diseases that include neurodegeneration. Several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis are characterized by protein aggregation, while an impaired DNA damage response (DDR) as in many genetic DNA repair disorders leads to pronounced neuropathological features. It remains unclear to what degree these cellular events interconnect with each other in the development of neurological diseases. This review highlights how the loss of protein homeostasis and genome instability influence one other. We will discuss studies that illustrate this connection. DNA damage contributes to many neurodegenerative diseases, as shown by an increased level of DNA damage in patients, possibly due to the effects of protein aggregates on chromatin, the sequestration of DNA repair proteins and novel putative DNA repair functions. Conversely, genome stability is also important for protein homeostasis. For example, gene copy number variations and the loss of key DDR components can lead to marked proteotoxic stress. An improved understanding of how protein homeostasis and genome stability are mechanistically connected is needed and promises to lead to the development of novel therapeutic interventions. |
| first_indexed | 2024-04-11T14:45:17Z |
| format | Article |
| id | doaj.art-9e62eec9c4c745558ac0b98994e49729 |
| institution | Directory Open Access Journal |
| issn | 2046-2441 |
| language | English |
| last_indexed | 2024-04-11T14:45:17Z |
| publishDate | 2021-04-01 |
| publisher | The Royal Society |
| record_format | Article |
| series | Open Biology |
| spelling | doaj.art-9e62eec9c4c745558ac0b98994e497292022-12-22T04:17:42ZengThe Royal SocietyOpen Biology2046-24412021-04-0111410.1098/rsob.200296Genome instability and loss of protein homeostasis: converging paths to neurodegeneration?Anna Ainslie0Wouter Huiting1Lara Barazzuol2Steven Bergink3Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The NetherlandsDepartment of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The NetherlandsDepartment of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The NetherlandsDepartment of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The NetherlandsGenome instability and loss of protein homeostasis are hallmark events of age-related diseases that include neurodegeneration. Several neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis are characterized by protein aggregation, while an impaired DNA damage response (DDR) as in many genetic DNA repair disorders leads to pronounced neuropathological features. It remains unclear to what degree these cellular events interconnect with each other in the development of neurological diseases. This review highlights how the loss of protein homeostasis and genome instability influence one other. We will discuss studies that illustrate this connection. DNA damage contributes to many neurodegenerative diseases, as shown by an increased level of DNA damage in patients, possibly due to the effects of protein aggregates on chromatin, the sequestration of DNA repair proteins and novel putative DNA repair functions. Conversely, genome stability is also important for protein homeostasis. For example, gene copy number variations and the loss of key DDR components can lead to marked proteotoxic stress. An improved understanding of how protein homeostasis and genome stability are mechanistically connected is needed and promises to lead to the development of novel therapeutic interventions.https://royalsocietypublishing.org/doi/10.1098/rsob.200296neurodegenerationDNA damagegenome stabilityprotein homeostasisprotein aggregation |
| spellingShingle | Anna Ainslie Wouter Huiting Lara Barazzuol Steven Bergink Genome instability and loss of protein homeostasis: converging paths to neurodegeneration? Open Biology neurodegeneration DNA damage genome stability protein homeostasis protein aggregation |
| title | Genome instability and loss of protein homeostasis: converging paths to neurodegeneration? |
| title_full | Genome instability and loss of protein homeostasis: converging paths to neurodegeneration? |
| title_fullStr | Genome instability and loss of protein homeostasis: converging paths to neurodegeneration? |
| title_full_unstemmed | Genome instability and loss of protein homeostasis: converging paths to neurodegeneration? |
| title_short | Genome instability and loss of protein homeostasis: converging paths to neurodegeneration? |
| title_sort | genome instability and loss of protein homeostasis converging paths to neurodegeneration |
| topic | neurodegeneration DNA damage genome stability protein homeostasis protein aggregation |
| url | https://royalsocietypublishing.org/doi/10.1098/rsob.200296 |
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