Evidence map›Paper›PMID 25305083›Full record

ArticleHuman molecular genetics2015

Rab11 modulates α-synuclein-mediated defects in synaptic transmission and behaviour.

Carlo Breda, Marie L Nugent, Jasper G Estranero, Charalambos P Kyriacou, Tiago F Outeiro, Joern R Steinert, Flaviano Giorgini

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

Article in Human molecular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
3.8field-weighted citation impact, top 6% 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

61 citing papers in PubMed, 102 citations in OpenAlex.

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  19. Neurons and Glia Interplay in α-Synucleinopathies.International journal of molecular sciences · 2021
    Review
  20. The Role of Cholesterol in α-Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease.Movement disorders : official journal of the Movement Disorder Society · 2021
    Review

1 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

7 authors at 3 institutions in 3 countries.

Carlo BredaDepartment of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK.
Marie L NugentDepartment of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK, MRC Toxicology Unit, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
Jasper G EstraneroDepartment of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK.
Charalambos P KyriacouDepartment of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK.
Tiago F OuteiroDepartment of NeuroDegeneration and Restorative Research, Center for Nanoscale Microscopy and Molecular Physiology of the Brain, University Medical Center Goettingen, Göttingen, Germany and Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisboa, Portugal.
Joern R SteinertMRC Toxicology Unit, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK.
Flaviano GiorginiDepartment of Genetics, University of Leicester, University Road, Leicester LE1 7RH, UK, fg36@le.ac.uk.
University of Leicester · GBMRC Toxicology Unit · GBNanoscale Microscopy and Molecular Physiology of the Brain Cluster of Excellence 171 — DFG Research Center 103 · DE

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council MC_U132681855Parkinson's UK G-1203
6 · The paper itself

Abstract

A central pathological hallmark of Parkinson's disease (PD) is the presence of proteinaceous depositions known as Lewy bodies, which consist largely of the protein α-synuclein (aSyn). Mutations, multiplications and polymorphisms in the gene encoding aSyn are associated with familial forms of PD and susceptibility to idiopathic PD. Alterations in aSyn impair neuronal vesicle formation/transport, and likely contribute to PD pathogenesis by neuronal dysfunction and degeneration. aSyn is functionally associated with several Rab family GTPases, which perform various roles in vesicle trafficking. Here, we explore the role of the endosomal recycling factor Rab11 in the pathogenesis of PD using Drosophila models of aSyn toxicity. We find that aSyn induces synaptic potentiation at the larval neuromuscular junction by increasing synaptic vesicle (SV) size, and that these alterations are reversed by Rab11 overexpression. Furthermore, Rab11 decreases aSyn aggregation and ameliorates several aSyn-dependent phenotypes in both larvae and adult fruit flies, including locomotor activity, degeneration of dopaminergic neurons and shortened lifespan. This work emphasizes the importance of Rab11 in the modulation of SV size and consequent enhancement of synaptic function. Our results suggest that targeting Rab11 activity could have a therapeutic value in PD.

Indexed as

Synaptic Transmissionalpha-SynucleinAnimalsBehavior, AnimalBrainDopaminergic NeuronsDrosophilaFemaleGene ExpressionModels, BiologicalNeuromuscular JunctionParkinson DiseasePhenotypeProtein Transportrab11 GTP-Binding Proteinsrab GTP-Binding Proteinsalpha-Synucleinrab11 GTP-Binding Proteinsrab GTP-Binding Proteins

Identifiers

PMID25305083
PMCPMC4986550
OpenAlexW2162360946

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.