Evidence map›Paper›PMID 27679481›Full record

ArticleBrain : a journal of neurology2016

A de novo compound targeting α-synuclein improves deficits in models of Parkinson's disease.

Wolfgang Wrasidlo, Igor F Tsigelny, Diana L Price, Garima Dutta, Edward Rockenstein, Thomas C Schwarz, Karin Ledolter, Douglas Bonhaus, Amy Paulino, Simona Eleuteri and 14 more

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

Article in Brain : a journal of neurology, 2016. 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 95 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 2 pooled it
10.1field-weighted citation impact, top 1% 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

95 citing papers in PubMed, 2 syntheses or guidelines pooled it, 152 citations in OpenAlex.

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  9. Montelukast alleviates neuroinflammation and improves motor functions in the line 61 model of Parkinson's disease: An exploratory study.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
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35 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 5 institutions in 3 countries.

Wolfgang Wrasidlo1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Igor F Tsigelny1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Diana L Price3 Neuropore Therapies, Inc., San Diego, CA 92121, USA.
Garima Dutta4 Department of Neurology, University of California, Los Angeles, CA, 90095-1769, USA.
Edward Rockenstein1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Thomas C Schwarz5 MFPL and University of Vienna, Vienna, Austria.
Karin Ledolter5 MFPL and University of Vienna, Vienna, Austria.
Douglas Bonhaus3 Neuropore Therapies, Inc., San Diego, CA 92121, USA.
Amy Paulino3 Neuropore Therapies, Inc., San Diego, CA 92121, USA.
Simona Eleuteri1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Åge A Skjevik2 San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093, USA.
Valentina L Kouznetsova7 Moores Cancer Center, University of California San Diego, La Jolla, CA, 92093, USA.
Brian Spencer1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Paula Desplats1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Tania Gonzalez-Ruelas1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Margarita Trejo-Morales1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Cassia R Overk1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA.
Stefan Winter8 EVER Neuropharma, Unterach, Austria.
Chunni Zhu4 Department of Neurology, University of California, Los Angeles, CA, 90095-1769, USA.
Marie-Francoise Chesselet4 Department of Neurology, University of California, Los Angeles, CA, 90095-1769, USA.
Dieter Meier3 Neuropore Therapies, Inc., San Diego, CA 92121, USA.
Herbert Moessler8 EVER Neuropharma, Unterach, Austria.
Robert Konrat5 MFPL and University of Vienna, Vienna, Austria.
Eliezer Masliah1 Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093, USA emasliah@UCSD.edu.
University of California, San Diego · USUniversity of California, Los Angeles · USUniversity of Vienna · ATEVER Neuro Pharma (Austria) · ATSan Diego Supercomputer Center · US

Funding

VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
a-synuclein clearance strategies for the treatment of Lewy body disease.R37AG018440 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MASLIAH, ELIEZER · 2006 to 2014
$2.7M
NIA NIH HHS P50 AG005131NIA NIH HHS R37 AG018440
6 · The paper itself

Abstract

Abnormal accumulation and propagation of the neuronal protein α-synuclein has been hypothesized to underlie the pathogenesis of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Here we report a de novo-developed compound (NPT100-18A) that reduces α-synuclein toxicity through a novel mechanism that involves displacing α-synuclein from the membrane. This compound interacts with a domain in the C-terminus of α-synuclein. The E83R mutation reduces the compound interaction with the 80-90 amino acid region of α-synuclein and prevents the effects of NPT100-18A. In vitro studies showed that NPT100-18A reduced the formation of wild-type α-synuclein oligomers in membranes, reduced the neuronal accumulation of α-synuclein, and decreased markers of cell toxicity. In vivo studies were conducted in three different α-synuclein transgenic rodent models. Treatment with NPT100-18A ameliorated motor deficits in mThy1 wild-type α-synuclein transgenic mice in a dose-dependent manner at two independent institutions. Neuropathological examination showed that NPT100-18A decreased the accumulation of proteinase K-resistant α-synuclein aggregates in the CNS and was accompanied by the normalization of neuronal and inflammatory markers. These results were confirmed in a mutant line of α-synuclein transgenic mice that is prone to generate oligomers. In vivo imaging studies of α-synuclein-GFP transgenic mice using two-photon microscopy showed that NPT100-18A reduced the cortical synaptic accumulation of α-synuclein within 1 h post-administration. Taken together, these studies support the notion that altering the interaction of α-synuclein with the membrane might be a feasible therapeutic approach for developing new disease-modifying treatments of Parkinson's disease and other synucleinopathies.

Indexed as

Drug Discoveryalpha-SynucleinAnimalsAntiparkinson AgentsBehavior, AnimalDisease Models, AnimalDose-Response Relationship, DrugHumansMiceMice, TransgenicParkinson Diseasealpha-SynucleinAntiparkinson Agentsalpha-synucleincellular mechanismsexperimental modelsParkinson’s diseasesynucleinopathy

Identifiers

PMID27679481
PMCPMC5840882
OpenAlexW2525228732

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.