Evidence map›Paper›PMID 33875010›Full record

ArticleMolecular brain2021

Pharmacological inhibition of nSMase2 reduces brain exosome release and α-synuclein pathology in a Parkinson's disease model.

Chunni Zhu, Tina Bilousova, Samantha Focht, Michael Jun, Chris Jean Elias, Mikhail Melnik, Sujyoti Chandra, Jesus Campagna, Whitaker Cohn, Asa Hatami and 3 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular brain, 2021. 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 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.5field-weighted citation impact, top 17% 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

21 citing papers in PubMed, 26 citations in OpenAlex.

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  13. Synucleinopathies: Intrinsic and Extrinsic Factors.Cell biochemistry and biophysics · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 1 institution in 1 country.

Chunni Zhu *Drug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Tina Bilousova *Drug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Samantha FochtDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Michael JunDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Chris Jean EliasDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Mikhail MelnikDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Sujyoti ChandraDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Jesus CampagnaDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Whitaker CohnDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Asa HatamiDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Patricia SpilmanDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA.
Karen Hoppens GylysSchool of Nursing, University of California, Los Angeles, CA, 90095, USA.
Varghese JohnDrug Discovery Lab, Department of Neurology, University of California, Los Angeles, CA, 90095, USA. VJohn@mednet.ucla.edu.ORCID http://orcid.org/0000-0001-7675-2426
University of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimWe have previously reported that cambinol (DDL-112), a known inhibitor of neutral sphingomyelinase-2 (nSMase2), suppressed extracellular vesicle (EV)/exosome production in vitro in a cell model and reduced tau seed propagation. The enzyme nSMase2 is involved in the production of exosomes carrying proteopathic seeds and could contribute to cell-to-cell transmission of pathological protein aggregates implicated in neurodegenerative diseases such as Parkinson's disease (PD). Here, we performed in vivo studies to determine if DDL-112 can reduce brain EV/exosome production and proteopathic alpha synuclein (αSyn) spread in a PD mouse model.

methodsThe acute effects of single-dose treatment with DDL-112 on interleukin-1β-induced extracellular vesicle (EV) release in brain tissue of Thy1-αSyn PD model mice and chronic effects of 5 week DDL-112 treatment on behavioral/motor function and proteinase K-resistant αSyn aggregates in the PD model were determined. RESULTS/DISCUSSION: In the acute study, pre-treatment with DDL-112 reduced EV/exosome biogenesis and in the chronic study, treatment with DDL-112 was associated with a reduction in αSyn aggregates in the substantia nigra and improvement in motor function. Inhibition of nSMase2 thus offers a new approach to therapeutic development for neurodegenerative diseases with the potential to reduce the spread of disease-specific proteopathic proteins.

Indexed as

alpha-SynucleinAnimalsBrainDisease Models, AnimalEnzyme InhibitorsExosomesMice, TransgenicNaphthalenesParkinson DiseaseProtein AggregatesPyrimidinonesSirtuinsSphingomyelin Phosphodiesterasealpha-SynucleincambinolEnzyme InhibitorsNaphthalenesProtein AggregatesPyrimidinonesSirtuinsSmpd3 protein, mouseSnca protein, mouseSphingomyelin PhosphodiesteraseAlpha-synucleinExosomesExtracellular vesiclesNeutral sphingomyelinase-2Parkinson’s disease

Identifiers

PMID33875010
PMCPMC8056538
OpenAlexW3156170939

What OpenQuestion 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 OpenQuestion graph.