ArticleBrain : a journal of neurology2022
Alpha-synuclein supports type 1 interferon signalling in neurons and brain tissue.
Article in Brain : a journal of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 42 citations in OpenAlex.
- Alpha-synuclein at the crossroads of host-virus interactions: immunological roles beyond the nervous system.Journal of virology · 2026Review
- The neuroimmune system and cognition.Nature immunology · 2026Review
- Longitudinal Repeatome Remodeling in Peripheral Blood Following Parkinson's Disease Diagnosis.Genes · 2026Article
- Antiviral innate immunity induces alpha synuclein phosphorylation at serine129 in neurons independent of aggregation.NPJ Parkinson's disease · 2026Article
- Revisiting the alpha-synuclein paradox in melanoma-Parkinson's disease connection: more than a tale of two cell fates.Cellular and molecular life sciences : CMLS · 2025Review
- Lack of functional STING modulates immunity but does not protect dopaminergic neurons in the alpha-synuclein pre-formed fibrils Parkinson's disease mouse model.NPJ Parkinson's disease · 2025Article
- Antiviral responses in peripheral and brain neurons.Current opinion in immunology · 2025Review
- BMP9 knockout impairs pulmonary vessel muscularisation and confers aberrant tamoxifen sensitivity.Angiogenesis · 2025Article
- Variants in Lrrk2 and Snca deficiency do not alter the course of primary encephalitis due to neurotropic reovirus T3D in newborn mice.PloS one · 2025Article
- Alpha-synuclein expression in neurons modulates Japanese encephalitis virus infection.Journal of virology · 2024Article
- Sex-specific biphasic alpha-synuclein response and alterations of interneurons in a COVID-19 hamster model.EBioMedicine · 2024Article
- Current trends in basic research on Parkinson's disease: from mitochondria, lysosome to α-synuclein.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Neurotropic virus infection and neurodegenerative diseases: Potential roles of autophagy pathway.CNS neuroscience & therapeutics · 2024Review
- Alpha-synuclein dynamics bridge Type-I Interferon response and SARS-CoV-2 replication in peripheral cells.Biological research · 2024Article
- The role of interferon signaling in neurodegeneration and neuropsychiatric disorders.Frontiers in psychiatry · 2024Review
- Infections in the Etiology of Parkinson's Disease and Synucleinopathies: A Renewed Perspective, Mechanistic Insights, and Therapeutic Implications.Journal of Parkinson's disease · 2024Review
- SARS-CoV-2 and Parkinson's Disease: A Review of Where We Are Now.Biomedicines · 2023Review
- Different pieces of the same puzzle: a multifaceted perspective on the complex biological basis of Parkinson's disease.NPJ Parkinson's disease · 2023Review
- Determining the Location of the α-Synuclein Dimer Interface Using Native Top-Down Fragmentation and Isotope Depletion-Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2023Article
- Controversial Properties of Amyloidogenic Proteins and Peptides: New Data in the COVID Era.Biomedicines · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.