{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:42:46Z","timestamp":1792172566076,"version":"4.4.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"VA Merit Award","award":["I01BX003863"],"award-info":[{"award-number":["I01BX003863"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 NS123431"],"award-info":[{"award-number":["R01 NS123431"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01 AI153724"],"award-info":[{"award-number":["R01 AI153724"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"NINDS","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Mammalian Synthetic Biology"},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/K017276\/1"],"award-info":[{"award-number":["MR\/K017276\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Anne Rowling Regenerative Neurology Clinic"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The protein alpha-synuclein is predominantly expressed in neurons and is associated with neurodegenerative diseases like Parkinson\u2019s 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.<\/jats:p>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>","DOI":"10.1093\/brain\/awac192","type":"journal-article","created":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T00:09:20Z","timestamp":1658362160000},"page":"3622-3636","source":"Crossref","is-referenced-by-count":45,"title":["Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue"],"prefix":"10.1093","volume":"145","author":[{"given":"Brendan","family":"Monogue","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"},{"name":"Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixi","family":"Chen","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine and the School of Biological Sciences, University of Edinburgh , Edinburgh EH16 4UU , UK"},{"name":"UK Centre for Mammalian Synthetic Biology, University of Edinburgh , Edinburgh EH16 4UU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadrian","family":"Sparks","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranya","family":"Behbehani","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine and the School of Biological Sciences, University of Edinburgh , Edinburgh EH16 4UU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Chai","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine and the School of Biological Sciences, University of Edinburgh , Edinburgh EH16 4UU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander J","family":"Rajic","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Massey","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B K","family":"Kleinschmidt-Demasters","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"},{"name":"Departments of Pathology and Neurosurgery, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Vermeren","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine and the School of Biological Sciences, University of Edinburgh , Edinburgh EH16 4UU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8805-7356","authenticated-orcid":false,"given":"Tilo","family":"Kunath","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine and the School of Biological Sciences, University of Edinburgh , Edinburgh EH16 4UU , UK"},{"name":"UK Centre for Mammalian Synthetic Biology, University of Edinburgh , Edinburgh EH16 4UU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9305-2683","authenticated-orcid":false,"given":"J David","family":"Beckham","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"},{"name":"Division of Infectious Diseases, Department of Medicine, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"},{"name":"Department of Neurology, University of Colorado Anschutz Medical Campus , Aurora, CO 80045 , USA"},{"name":"Rocky Mountain Regional VA Medical Center , Aurora, CO 80045 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,7,18]]},"reference":[{"key":"2023060106301589100_awac192-B1","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/j.1749-6632.2000.tb06900.x","article-title":"The \u03b1-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy","volume":"920","author":"Spillantini","year":"2000","journal-title":"Ann N Y Acad Sci"},{"key":"2023060106301589100_awac192-B2","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0166-2236(97)01213-7","article-title":"The 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