دورية أكاديمية
Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue.
| العنوان: | Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue. |
|---|---|
| المؤلفون: | Monogue, Brendan, Chen, Yixi, Sparks, Hadrian, Behbehani, Ranya, Chai, Andrew, Rajic, Alexander J, Massey, Aaron, Kleinschmidt-Demasters, B K, Vermeren, Matthieu, Kunath, Tilo, Beckham, J David |
| المصدر: | Brain ; ISSN:1460-2156 ; Volume:145 ; Issue:10 |
| بيانات النشر: | Silverchair Information Systems |
| سنة النشر: | 2022 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | alpha-synuclein, brain, interferon, neuron, virus |
| الوصف: | The protein alpha-synuclein is predominantly expressed in neurons and is associated with neurodegenerative diseases like Parkinson's disease and dementia with Lewy bodies. However, the normal function of alpha-synuclein in neurons is not clearly defined. We have previously shown that mice lacking alpha-synuclein expression exhibit markedly increased viral growth in the brain, increased mortality and increased neuronal cell death, implicating alpha-synuclein in the neuronal innate immune response. To investigate the mechanism of alpha-synuclein-induced immune responses to viral infections in the brain, we challenged alpha-synuclein knockout mice and human alpha-synuclein knockout dopaminergic neurons with RNA virus infection and discovered that alpha-synuclein is required for neuronal expression of interferon-stimulated genes. Furthermore, human alpha-synuclein knockout neurons treated with type 1 interferon failed to induce a broad range of interferon stimulated genes, implying that alpha-synuclein interacts with type 1 interferon signalling. We next found that alpha-synuclein accumulates in the nucleus of interferon-treated human neurons after interferon treatment and we demonstrated that interferon-mediated phosphorylation of STAT2 is dependent on alpha-synuclein expression in human neurons. Next, we found that activated STAT2 co-localizes with alpha-synuclein following type 1 interferon stimulation in neurons. Finally, we found that brain tissue from patients with viral encephalitis expresses increased levels of phospho-serine129 alpha-synuclein in neurons. Taken together, our results show that alpha-synuclein expression supports neuron-specific interferon responses by localizing to the nucleus, supporting STAT2 activation, co-localizing with phosphorylated STAT2 in neurons and supporting expression of interferon-stimulated genes. These data provide a novel mechanism that links interferon activation and alpha-synuclein function in neurons. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1093/brain/awac192Test; https://pubmed.ncbi.nlm.nih.gov/35858675Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233298Test/ |
| DOI: | 10.1093/brain/awac192 |
| الإتاحة: | https://doi.org/10.1093/brain/awac192Test https://pubmed.ncbi.nlm.nih.gov/35858675Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233298Test/ |
| حقوق: | © The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. |
| رقم الانضمام: | edsbas.47077E48 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1093/brain/awac192 |
|---|