Evidence map›Paper›PMID 28827786›Full record

ArticleScientific reports2017

Excess α-synuclein compromises phagocytosis in iPSC-derived macrophages.

Walther Haenseler, Federico Zambon, Heyne Lee, Jane Vowles, Federica Rinaldi, Galbha Duggal, Henry Houlden, Katrina Gwinn, Selina Wray, Kelvin C Luk and 3 more

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

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.

0numbers the graph read from it
0cells of the map it votes in
86citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

86 citing papers in PubMed, 118 citations in OpenAlex.

  1. Article
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  8. Peripheral SNCADiscover oncology · 2025
    Article
  9. Review
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  12. Article
  13. Current Development of iPSC-Based Modeling in Neurodegenerative Diseases.International journal of molecular sciences · 2025
    Review
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  17. Article
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26 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

13 authors at 4 institutions in 2 countries.

Walther HaenselerJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK. hwalther@gmx.ch.
Federico ZambonDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.
Heyne LeeJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
Jane VowlesJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
Federica RinaldiJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
Galbha DuggalNuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DS, UK.
Henry HouldenDepartment of Molecular Neuroscience, University College London Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Katrina GwinnNational Institutes of Health, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.ORCID 0000-0002-8277-651X
Selina WrayDepartment of Molecular Neuroscience, University College London Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Kelvin C LukDepartment of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.ORCID 0000-0002-6591-6269
Richard Wade-MartinsDepartment of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford, OX1 3QX, UK.
William S JamesJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK.
Sally A CowleyJames Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford, OX1 3RE, UK. sally.cowley@path.ox.ac.uk.ORCID 0000-0003-0297-6675
University of Oxford · GBNational Hospital for Neurology and Neurosurgery · GBNational Institutes of Health · USUniversity of Pennsylvania · US

Funding

Medical Research Council G0900747Medical Research Council MC_EX_MR/N50192X/1Medical Research Council MR/L023784/1Medical Research Council MR/L023784/2Medical Research Council MR/M024962/1Parkinson's UK J-0901Wellcome Trust WTISSF121302
6 · The paper itself

Abstract

To examine the pathogenic role of α-synuclein (αS) in Parkinson's Disease, we have generated induced Pluripotent Stem Cell lines from early onset Parkinson's Disease patients with SNCA A53T and SNCA Triplication mutations, and in this study have differentiated them to PSC-macrophages (pMac), which recapitulate many features of their brain-resident cousins, microglia. We show that SNCA Triplication pMac, but not A53T pMac, have significantly increased intracellular αS versus controls and release significantly more αS to the medium. SNCA Triplication pMac, but not A53T pMac, show significantly reduced phagocytosis capability and this can be phenocopied by adding monomeric αS to the cell culture medium of control pMac. Fibrillar αS is taken up by pMac by actin-rearrangement-dependent pathways, and monomeric αS by actin-independent pathways. Finally, pMac degrade αS and this can be arrested by blocking lysosomal and proteasomal pathways. Together, these results show that macrophages are capable of clearing αS, but that high levels of exogenous or endogenous αS compromise this ability, likely a vicious cycle scenario faced by microglia in Parkinson's disease.

Indexed as

AdultAgedAged, 80 and overalpha-SynucleinCell DifferentiationFemaleGene DosageHumansMacrophagesMaleMiddle AgedMutation, MissenseParkinson DiseasePhagocytosisPluripotent Stem Cellsalpha-SynucleinSNCA protein, human

Identifiers

PMID28827786
PMCPMC5567139
OpenAlexW2745862042

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.