Evidence map›Paper›PMID 28585223›Full record

ArticleNeurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics2017

A Molecular Tweezer Ameliorates Motor Deficits in Mice Overexpressing α-Synuclein.

Franziska Richter, Sudhakar R Subramaniam, Iddo Magen, Patrick Lee, Jane Hayes, Aida Attar, Chunni Zhu, Nicholas R Franich, Nicholas Bove, Krystal De La Rosa and 5 more

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

Article in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.7field-weighted citation impact, top 5% 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

32 citing papers in PubMed, 59 citations in OpenAlex.

  1. Article
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  8. A Mouse Model to Test Novel Therapeutics for Parkinson's Disease: an Update on the Thy1-aSyn ("line 61") Mice.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  9. Article
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  15. The Role of α-Synuclein Oligomers in Parkinson's Disease.International journal of molecular sciences · 2020
    Review
  16. Article
  17. Article
  18. The Amyloid Inhibitor CLR01 Relieves Autophagy and Ameliorates Neuropathology in a Severe Lysosomal Storage Disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2020
    Article
  19. 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

15 authors at 2 institutions in 2 countries.

Franziska RichterDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Sudhakar R SubramaniamDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Iddo MagenDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Patrick LeeDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jane HayesDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Aida AttarDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Chunni ZhuDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Nicholas R FranichDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Nicholas BoveDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Krystal De La RosaDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Jacky KwongDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA.
Frank-Gerrit KlärnerInstitute of Organic Chemistry, University of Duisburg-Essen, Essen, Germany.
Thomas SchraderInstitute of Organic Chemistry, University of Duisburg-Essen, Essen, Germany.
Marie-Françoise ChesseletDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. mchesselet@mednet.ucla.edu.
Gal BitanDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. gbitan@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Duisburg-Essen · DE

Funding

UCLA CENTER FOR THE STUDY OF PARKINSON'S DISEASEP50NS038367 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHESSELET, MARIE-FRANCOISE S · 1999 to 2011
$15.3M
Project 4: Pesticides and Genes In PD: Studies In HumansP01ES016732 · NIEHS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI RITZ, BEATE R. · 2008 to 2012
$6.7M
Michael J. Fox Foundation for Parkinson's Research RRIA AwardNational Institute of Neurological Disorders and Stroke ES016732National Institute of Neurological Disorders and Stroke NS38367NIEHS NIH HHS P01 ES016732NINDS NIH HHS P50 NS038367RJG Foundation 20095024
6 · The paper itself

Abstract

Aberrant accumulation and self-assembly of α-synuclein are tightly linked to several neurodegenerative diseases called synucleinopathies, including idiopathic Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Deposition of fibrillar α-synuclein as insoluble inclusions in affected brain cells is a pathological hallmark of synucleinopathies. However, water-soluble α-synuclein oligomers may be the actual culprits causing neuronal dysfunction and degeneration in synucleinopathies. Accordingly, therapeutic approaches targeting the toxic α-synuclein assemblies are attractive for these incurable disorders. The "molecular tweezer" CLR01 selectively remodels abnormal protein self-assembly through reversible binding to Lys residues. Here, we treated young male mice overexpressing human wild-type α-synuclein under control of the Thy-1 promoter (Thy1-aSyn mice) with CLR01 and examined motor behavior and α-synuclein in the brain. Intracerebroventricular administration of CLR01 for 28 days to the mice improved motor dysfunction in the challenging beam test and caused a significant decrease of buffer-soluble α-synuclein in the striatum. Proteinase-K-resistant, insoluble α-synuclein deposits remained unchanged in the substantia nigra, whereas levels of diffuse cytoplasmic α-synuclein in dopaminergic neurons increased in mice receiving CLR01 compared with vehicle. More moderate improvement of motor deficits was also achieved by subcutaneous administration of CLR01, in 2/5 trials of the challenging beam test and in the pole test, which requires balance and coordination. The data support further development of molecular tweezers as therapeutic agents for synucleinopathies.

Indexed as

alpha-SynucleinAnimalsBlood-Brain BarrierBrainBridged-Ring CompoundsDopaminergic NeuronsHumansInjections, IntraventricularMaleMice, Inbred C57BLMice, TransgenicMotor ActivityOrganophosphatesTyrosine 3-Monooxygenasealpha-SynucleinBridged-Ring CompoundsCLR01 compoundOrganophosphatesTyrosine 3-Monooxygenasedrug testingmotor behaviormouse modelParkinson’s diseasesynucleinopathiesα-synuclein aggregation

Identifiers

PMID28585223
PMCPMC5722755
OpenAlexW2623393864

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.