Evidence map›Paper›PMID 33760024›Full record

ArticleBrain : a journal of neurology2021

CSPα reduces aggregates and rescues striatal dopamine release in α-synuclein transgenic mice.

Laura Caló, Eric Hidari, Michal Wegrzynowicz, Jeffrey W Dalley, Bernard L Schneider, Martyna Podgajna, Oleg Anichtchik, Emma Carlson, David Klenerman, Maria Grazia Spillantini

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

Article in Brain : a journal of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 13% 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

15 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
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  6. Decoding transcriptomic signatures of cysteine string protein alpha-mediated synapse maintenance.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  7. Article
  8. Review
  9. Review
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  12. Synapsin III gene silencing redeems alpha-synuclein transgenic mice from Parkinson's disease-like phenotype.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Article
  13. CSPα in neurodegenerative diseases.Frontiers in aging neuroscience · 2022
    Review
  14. Article
  15. Review
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

10 authors at 3 institutions in 3 countries.

Laura CalóDepartment of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, UK.
Eric HidariDementia Research Institute, University of Cambridge, Cambridge, UK.ORCID 0000-0002-4777-5239
Michal WegrzynowiczDepartment of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, UK.ORCID 0000-0002-5082-9576
Jeffrey W DalleyDepartment of Psychology, University of Cambridge, Cambridge, UK.
Bernard L SchneiderBrain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Martyna PodgajnaLaboratory of Molecular Basis of Neurodegeneration, Mossakowski Medical Research Institute, Polish Academy of Sciences, Warsaw, Poland.ORCID 0000-0002-8323-9492
Oleg AnichtchikDepartment of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, UK.
Emma CarlsonDepartment of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, UK.
David KlenermanDementia Research Institute, University of Cambridge, Cambridge, UK.
Maria Grazia SpillantiniDepartment of Clinical Neurosciences, Clifford Allbutt Building, University of Cambridge, Cambridge, UK.
University of Cambridge · GBÉcole Polytechnique Fédérale de Lausanne · CHPolish Academy of Sciences · PL

Funding

Medical Research CouncilParkinson's UK G-0701Parkinson's UK G-1102Parkinson's UK G-1703
6 · The paper itself

Abstract

α-Synuclein aggregation at the synapse is an early event in Parkinson's disease and is associated with impaired striatal synaptic function and dopaminergic neuronal death. The cysteine string protein (CSPα) and α-synuclein have partially overlapping roles in maintaining synaptic function and mutations in each cause neurodegenerative diseases. CSPα is a member of the DNAJ/HSP40 family of co-chaperones and like α-synuclein, chaperones the SNARE complex assembly and controls neurotransmitter release. α-Synuclein can rescue neurodegeneration in CSPαKO mice. However, whether α-synuclein aggregation alters CSPα expression and function is unknown. Here we show that α-synuclein aggregation at the synapse is associated with a decrease in synaptic CSPα and a reduction in the complexes that CSPα forms with HSC70 and STGa. We further show that viral delivery of CSPα rescues in vitro the impaired vesicle recycling in PC12 cells with α-synuclein aggregates and in vivo reduces synaptic α-synuclein aggregates increasing monomeric α-synuclein and restoring normal dopamine release in 1-120hαSyn mice. These novel findings reveal a mechanism by which α-synuclein aggregation alters CSPα at the synapse, and show that CSPα rescues α-synuclein aggregation-related phenotype in 1-120hαSyn mice similar to the effect of α-synuclein in CSPαKO mice. These results implicate CSPα as a potential therapeutic target for the treatment of early-stage Parkinson's disease.

Indexed as

alpha-SynucleinAnimalsCorpus StriatumDopamineHSP40 Heat-Shock ProteinsMembrane ProteinsMiceMice, Inbred C57BLMice, TransgenicParkinson DiseaseProtein Aggregation, PathologicalSynapsesalpha-Synucleincysteine string proteinDopamineHSP40 Heat-Shock ProteinsMembrane ProteinsCSPαDNAJ chaperone familyParkinson’s diseasesynapseα-synuclein

Identifiers

PMID33760024
PMCPMC8320296
OpenAlexW3113312909

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.