Evidence map›Paper›PMID 26905200›Full record

ArticleStem cell reports2016

ER Stress and Autophagic Perturbations Lead to Elevated Extracellular α-Synuclein in GBA-N370S Parkinson's iPSC-Derived Dopamine Neurons.

Hugo J R Fernandes, Elizabeth M Hartfield, Helen C Christian, Evangelia Emmanoulidou, Ying Zheng, Heather Booth, Helle Bogetofte, Charmaine Lang, Brent J Ryan, S Pablo Sardi and 10 more

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

Article in Stem cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers.

0numbers the graph read from it
0cells of the map it votes in
228citing papers in PubMed
21.2field-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

228 citing papers in PubMed, 358 citations in OpenAlex.

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  19. p.N370SInternational journal of molecular sciences · 2025
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168 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

20 authors at 3 institutions in 3 countries.

Hugo J R FernandesOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Elizabeth M HartfieldOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Helen C ChristianDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Evangelia EmmanoulidouDivision of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens 11526, Greece.
Ying ZhengOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Nuffield Department of Clinical Medicine, Division of Clinical Neurology, University of Oxford, Oxford OX3 9DU, UK.
Heather BoothOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Helle BogetofteOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Institute of Molecular Medicine, University of Southern Denmark, Odense 5230, Denmark.
Charmaine LangOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Brent J RyanOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
S Pablo SardiGenzyme, a Sanofi Company, Framingham, MA 01701, USA.
Jennifer BadgerOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Jane VowlesOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; The James Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Samuel EvettsOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Nuffield Department of Clinical Medicine, Division of Clinical Neurology, University of Oxford, Oxford OX3 9DU, UK.
George K TofarisOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Nuffield Department of Clinical Medicine, Division of Clinical Neurology, University of Oxford, Oxford OX3 9DU, UK.
Kostas VekrellisDivision of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens 11526, Greece.
Kevin TalbotOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Nuffield Department of Clinical Medicine, Division of Clinical Neurology, University of Oxford, Oxford OX3 9DU, UK.
Michele T HuOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Nuffield Department of Clinical Medicine, Division of Clinical Neurology, University of Oxford, Oxford OX3 9DU, UK.
William JamesOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; The James Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Sally A CowleyOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; The James Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
Richard Wade-MartinsOxford Parkinson's Disease Centre, University of Oxford, South Parks Road, Oxford OX1 3QX, UK; Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK. Electronic address: richard.wade-martins@dpag.ox.ac.uk.
University of Oxford · GBBiomedical Research Foundation of the Academy of Athens · GRUniversity of Southern Denmark · DK

Funding

Medical Research Council G090074791070Medical Research Council MC_EX_MR/N50192X/1Medical Research Council MR/L023784/1Medical Research Council MR/L023784/2Medical Research Council MR/M024962/1Parkinson's UK H-1102Parkinson's UK J-0901Wellcome Trust 090532/Z/09/ZWellcome Trust WT082260/Z/07/Z
6 · The paper itself

Abstract

Heterozygous mutations in the glucocerebrosidase gene (GBA) represent the strongest common genetic risk factor for Parkinson's disease (PD), the second most common neurodegenerative disorder. However, the molecular mechanisms underlying this association are still poorly understood. Here, we have analyzed ten independent induced pluripotent stem cell (iPSC) lines from three controls and three unrelated PD patients heterozygous for the GBA-N370S mutation, and identified relevant disease mechanisms. After differentiation into dopaminergic neurons, we observed misprocessing of mutant glucocerebrosidase protein in the ER, associated with activation of ER stress and abnormal cellular lipid profiles. Furthermore, we observed autophagic perturbations and an enlargement of the lysosomal compartment specifically in dopamine neurons. Finally, we found increased extracellular α-synuclein in patient-derived neuronal culture medium, which was not associated with exosomes. Overall, ER stress, autophagic/lysosomal perturbations, and elevated extracellular α-synuclein likely represent critical early cellular phenotypes of PD, which might offer multiple therapeutic targets.

Indexed as

AutophagyEndoplasmic Reticulum Stressalpha-SynucleinAnimalsCell LineCells, CulturedDopaminergic NeuronsExosomesGlucosylceramidaseHumansInduced Pluripotent Stem CellsLysosomesMiceMutation, MissenseNeurogenesisParkinson Diseasealpha-SynucleinGlucosylceramidase

Identifiers

PMID26905200
PMCPMC4788783
OpenAlexW2277130721

What OpenQuestion holds

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Registered trials

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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.