Evidence map›Paper›PMID 37704739›Full record

ArticleScientific reports2023

Viral-like TLR3 induction of cytokine networks and α-synuclein are reduced by complement C3 blockade in mouse brain.

Ria Thomas, Kyle J Connolly, Oeystein R Brekk, Anthony J Hinrich, Michelle L Hastings, Ole Isacson, Penelope J Hallett

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
2.1field-weighted citation impact, top 12% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 17 citations in OpenAlex.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 1 country.

Ria Thomas *Neuroregeneration Institute, McLean Hospital/Harvard Medical School, Belmont, MA, 02478, USA.
Kyle J Connolly *Neuroregeneration Institute, McLean Hospital/Harvard Medical School, Belmont, MA, 02478, USA.
Oeystein R BrekkNeuroregeneration Institute, McLean Hospital/Harvard Medical School, Belmont, MA, 02478, USA.
Anthony J HinrichCenter for Genetic Diseases, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064, USA.
Michelle L HastingsCenter for Genetic Diseases, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, 60064, USA.
Ole IsacsonNeuroregeneration Institute, McLean Hospital/Harvard Medical School, Belmont, MA, 02478, USA. ole_isacson@hms.harvard.edu.
Penelope J HallettNeuroregeneration Institute, McLean Hospital/Harvard Medical School, Belmont, MA, 02478, USA. phallett@mclean.harvard.edu.
McLean Hospital · USHarvard University · USRosalind Franklin University of Medicine and Science · US

Funding

Prevention of complement and immune-mediated Lewy body dementiaR01AG060195 · NIA · MCLEAN HOSPITAL · PI HALLETT, PENELOPE JANE, HASTINGS, MICHELLE L · 2018 to 2022
$2.9M
NIA NIH HHS R01 AG060195
6 · The paper itself

Abstract

Inflammatory processes and mechanisms are of central importance in neurodegenerative diseases. In the brain, α-synucleinopathies such as Parkinson's disease (PD) and Lewy body dementia (LBD) show immune cytokine network activation and increased toll like receptor 3 (TLR3) levels for viral double-stranded RNA (dsRNA). Brain inflammatory reactions caused by TLR3 activation are also relevant to understand pathogenic cascades by viral SARS-CoV-2 infection causing post- COVID-19 brain-related syndromes. In the current study, following regional brain TLR3 activation induced by dsRNA in mice, an acute complement C3 response was seen at 2 days. A C3 splice-switching antisense oligonucleotide (ASO) that promotes the splicing of a non-productive C3 mRNA, prevented downstream cytokines, such as IL-6, and α-synuclein changes. This report is the first demonstration that α-synuclein increases occur downstream of complement C3 activation. Relevant to brain dysfunction, post-COVID-19 syndromes and pathological changes leading to PD and LBD, viral dsRNA TLR3 activation in the presence of C3 complement blockade further revealed significant interactions between complement systems, inflammatory cytokine networks and α-synuclein changes.

Indexed as

COVID-19Lewy Body DiseaseParkinson Diseasealpha-SynucleinAnimalsBrainComplement C3CytokinesMiceRNA, Double-StrandedSARS-CoV-2SyndromeToll-Like Receptor 3alpha-SynucleinComplement C3CytokinesRNA, Double-StrandedSnca protein, mouseTLR3 protein, mouseToll-Like Receptor 3

Identifiers

PMID37704739
PMCPMC10499893
OpenAlexW4386697184

What Socratic holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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 Socratic graph.