Evidence map›Paper›PMID 41186731›Full record

ArticleActa neuropathologica2025

Intracellular trafficking SNARE protein, syntaxin-6, modifies prion cellular phenotypes and risk of disease development in vivo.

Elizabeth Hill, Mitali M Patel, Juan M Ribes, Jacqueline Linehan, Fuquan Zhang, Tatiana Jakubcova, Shyma Hamdan, Andrew Tomlinson, Tiziana Ercolani, Christian Schmidt and 13 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Acta neuropathologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Elizabeth HillMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Mitali M PatelMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Juan M RibesMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Jacqueline LinehanMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Fuquan ZhangMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Tatiana JakubcovaMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Shyma HamdanMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Andrew TomlinsonMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Tiziana ErcolaniMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Christian SchmidtMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Parvin AhmedMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
George ThirlwayMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Fabio ArgentinaMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Aline T MarinhoMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Emma JonesSchool of Biochemistry, Biomedical Sciences Building, University of Bristol, Bristol, BS8 1TD, UK.
Nicholas KayeMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Craig FitzhughMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Graham S JacksonMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Sebastian BrandnerMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Peter-Christian KlöhnMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
John CollingeMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Thomas J CunninghamMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK.
Simon MeadMRC Prion Unit at UCL, UCL Institute of Prion Diseases, Courtauld Building, 33 Cleveland Street, London, W1W 7FF, UK. s.mead@prion.ucl.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Increased expression of syntaxin-6, a SNARE protein involved in intracellular protein trafficking, is a proposed genetic risk mechanism for sporadic prion disease and progressive supranuclear palsy, as well as being implicated in Alzheimer's disease. However, no study has validated its functional role in prion disease, its mechanism of action nor explored the disease stage at which it is acting. Here, we show that syntaxin-6 knockdown in cellular models increases cell-associated infectivity, whilst overexpression produces the opposite effect. This observation is broadly consistent across multiple cell types and prion strains. Furthermore, syntaxin-6 knockdown leads to an accumulation of perinuclear disease-related PrP, consistent with a trafficking mechanism, and alters the morphology of disease-related PrP. We demonstrate that syntaxin-6 knockdown reduces the secretion of prions from infected cells, which provides a mechanism for the prion-related cellular phenotypes observed. Complementary in vivo studies showed that syntaxin-6 influences early stages of prion disease in experimental mice, increasing transmission risk after inoculation with low prion doses. Conversely, syntaxin-6 does not affect prion propagation kinetics or toxicity during established disease. Taken together, our studies firmly establish syntaxin-6 as a modifier of prion pathogenesis with a role in prion trafficking and export. Our findings further suggest that syntaxin-6 modifies the risk of the establishment of disease in line with its genetic association in humans. Thus, this work provides important insights into the role of a pleiotropic prion/prion-like modifier, grounded in human genetics evidence, which may have wider relevance to other neurodegenerative diseases.

Indexed as

Prion DiseasesPrionsQa-SNARE ProteinsAnimalsDisease Models, AnimalHumansMiceMice, Inbred C57BLPhenotypeProtein TransportPrionsQa-SNARE ProteinsCreutzfeldt–Jakob diseaseFunctional geneticsNeurodegenerationPrion diseasePrion-like mechanisms

Identifiers

PMID41186731
PMCPMC12586215

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.