Evidence map›Paper›PMID 25505180›Full record

ArticleThe Journal of biological chemistry2015

The neutral sphingomyelinase pathway regulates packaging of the prion protein into exosomes.

Belinda B Guo, Shayne A Bellingham, Andrew F Hill

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

150 citing papers in PubMed, 227 citations in OpenAlex.

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  16. Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025
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90 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Belinda B GuoFrom the Department of Biochemistry and Molecular Biology, The University of Melbourne, VIC 3010, Australia and the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia.
Shayne A BellinghamFrom the Department of Biochemistry and Molecular Biology, The University of Melbourne, VIC 3010, Australia and the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia shayneb@unimelb.edu.au.
Andrew F HillFrom the Department of Biochemistry and Molecular Biology, The University of Melbourne, VIC 3010, Australia and the Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia a.hill@unimelb.edu.au.
University of Melbourne · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Prion diseases are a group of transmissible, fatal neurodegenerative disorders associated with the misfolding of the host-encoded prion protein, PrP(C), into a disease-associated form, PrP(Sc). The transmissible prion agent is principally formed of PrP(Sc) itself and is associated with extracellular vesicles known as exosomes. Exosomes are released from cells both in vitro and in vivo, and have been proposed as a mechanism by which prions spread intercellularly. The biogenesis of exosomes occurs within the endosomal system, through formation of intraluminal vesicles (ILVs), which are subsequently released from cells as exosomes. ILV formation is known to be regulated by the endosomal sorting complexes required for transport (ESCRT) machinery, although an alternative neutral sphingomyelinase (nSMase) pathway has been suggested to also regulate this process. Here, we investigate a role for the nSMase pathway in exosome biogenesis and packaging of PrP into these vesicles. Inhibition of the nSMase pathway using GW4869 revealed a role for the nSMase pathway in both exosome formation and PrP packaging. In agreement, targeted knockdown of nSMase1 and nSMase2 in mouse neurons using lentivirus-mediated RNAi also decreases exosome release, demonstrating the nSMase pathway regulates the biogenesis and release of exosomes. We also demonstrate that PrP(C) packaging is dependent on nSMase2, whereas the packaging of disease-associated PrP(Sc) into exosomes occurs independently of nSMase2. These findings provide further insight into prion transmission and identify a pathway which directly assists exosome-mediated transmission of prions.

Indexed as

AnimalsCell LineExosomesHumansMiceNeuronsPrionsSphingomyelin PhosphodiesterasePrionsSmpd3 protein, mouseSphingomyelin PhosphodiesteraseCeramideExosomeExosomesExtracellular VesiclesNeutral SphingomyelinasenSMase2PrionPrion Disease

Identifiers

PMID25505180
PMCPMC4319014
OpenAlexW1970413727

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.