Evidence map›Paper›PMID 34107263›Full record

ArticleCell reports2021

An integrated genomic approach to dissect the genetic landscape regulating the cell-to-cell transfer of α-synuclein.

Eleanna Kara, Alessandro Crimi, Anne Wiedmer, Marc Emmenegger, Claudia Manzoni, Sara Bandres-Ciga, Karishma D'Sa, Regina H Reynolds, Juan A Botía, Marco Losa and 23 more

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

Article in Cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.0field-weighted citation impact, top 22% 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

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. LRP10 and α-synuclein transmission in Lewy body diseases.Cellular and molecular life sciences : CMLS · 2024
    Article
  7. Review
  8. Article
  9. Article
  10. Article
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

33 authors at 9 institutions in 6 countries.

Eleanna KaraInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland; Department of Neurodegenerative disease, University College London, London WC1N 3BG, UK.
Alessandro CrimiInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Anne WiedmerInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Marc EmmeneggerInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Claudia ManzoniDepartment of Pharmacology, University College London School of Pharmacy, London WC1N 1AX, UK; School of Pharmacy, University of Reading, Reading RG6 6AP, UK.
Sara Bandres-CigaLaboratory of Neurogenetics, National Institutes of Health, Bethesda, MD 20814, USA.
Karishma D'SaThe Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Department of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK; Department of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK.
Regina H ReynoldsDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.
Juan A BotíaDepartment of Neurodegenerative disease, University College London, London WC1N 3BG, UK; Departamento de Ingeniería de la Información y las Comunicaciones, Universidad de Murcia, Murcia 30100, Spain.
Marco LosaInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Veronika LysenkoDepartment of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich 8091, Switzerland.
Manfredi CartaInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Daniel HeinzerInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Merve AvarInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Andra ChincisanInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Cornelis BlauwendraatLaboratory of Neurogenetics, National Institutes of Health, Bethesda, MD 20814, USA.
Sonia García-RuizDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.
Daniel PeaseInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Lorene MottierInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Alessandra CarrellaInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Dezirae Beck-SchneiderInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Andreia D MagalhãesInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland.
Caroline AemiseggerCenter for Microscopy and Image Analysis, University of Zurich, Zurich 8057, Switzerland.
Alexandre P A TheocharidesDepartment of Medical Oncology and Hematology, University Hospital Zurich and University of Zurich, Zurich 8091, Switzerland.
Zhanyun FanDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Jordan D MarksDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA; Mayo Clinic Alix School of Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Sarah C HoppDepartment of Pharmacology, UT Health San Antonio, San Antonio, TX 78229, USA; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, TX 78229, USA.
Andrey Y AbramovDepartment of Clinical and Movement Neurosciences, UCL Queen Square Institute of Neurology, London WC1N 3BG, UK.
Patrick A LewisDepartment of Neurodegenerative disease, University College London, London WC1N 3BG, UK; School of Pharmacy, University of Reading, Reading RG6 6AP, UK; Department of Comparative Biomedical Sciences, Royal Veterinary College, London NW1 0TU, UK.
Mina RytenDepartment of Genetics and Genomic Medicine, Great Ormond Street Institute of Child Health, University College London, London, UK; NIHR Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK.
John HardyDepartment of Neurodegenerative disease, University College London, London WC1N 3BG, UK; UK Dementia Research Institute, University College London, London WC1N 3BG, UK; Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK; Institute for Advanced Study, the Hong Kong University of Science and Technology, Hong Kong SAR, China.
Bradley T HymanDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA.
Adriano AguzziInstitute of Neuropathology, University of Zurich and University Hospital Zurich, Zurich 8091, Switzerland. Electronic address: adriano.aguzzi@usz.ch.
University of Zurich · CHGreat Ormond Street Hospital · GBHarvard University · USNational Institutes of Health · USUniversity College London · GBHong Kong University of Science and Technology · HKNational Hospital for Neurology and Neurosurgery · GBRoyal Veterinary College · GBThe University of Texas Health Science Center at San Antonio · US

Funding

Genome wide SNP analysis in Parkinson's diseaseZ01AG000949 · NIA · NATIONAL INSTITUTE ON AGING · PI SINGLETON, ANDREW B · 2006 to 2008
$2.6M
Prospective studies on Parkinson's diseaseZ01ES101986 · NIEHS · NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES · PI CHEN, HONGLEI · 2006 to 2008
$1.2M
Intramural NIH HHS Z01 AG000949Intramural NIH HHS Z01 ES101986Medical Research Council G0701075Medical Research Council G0901254Medical Research Council G1001253Medical Research Council MR/J004758/1Medical Research Council MR/K01417X/1Medical Research Council MR/L012758/1Medical Research Council MR/L501542/1Medical Research Council MR/N008324/1Medical Research Council MR/N026004/1Parkinson's UK G-0907Parkinson's UK G-1307Wellcome TrustWellcome Trust 202903/Z/16/Z
6 · The paper itself

Abstract

Neuropathological and experimental evidence suggests that the cell-to-cell transfer of α-synuclein has an important role in the pathogenesis of Parkinson's disease (PD). However, the mechanism underlying this phenomenon is not fully understood. We undertook a small interfering RNA (siRNA), genome-wide screen to identify genes regulating the cell-to-cell transfer of α-synuclein. A genetically encoded reporter, GFP-2A-αSynuclein-RFP, suitable for separating donor and recipient cells, was transiently transfected into HEK cells stably overexpressing α-synuclein. We find that 38 genes regulate the transfer of α-synuclein-RFP, one of which is ITGA8, a candidate gene identified through a recent PD genome-wide association study (GWAS). Weighted gene co-expression network analysis (WGCNA) and weighted protein-protein network interaction analysis (WPPNIA) show that those hits cluster in networks that include known PD genes more frequently than expected by random chance. The findings expand our understanding of the mechanism of α-synuclein spread.

Indexed as

alpha-SynucleinCell CommunicationGenome-Wide Association StudyHumansProtein Interaction Mapsalpha-SynucleinBraak hypothesisGWAShigh-throughput screenITGA8siRNAweighted gene co-expression network analysisweighted protein-protein network interaction analysisα-synuclein

Identifiers

PMID34107263
PMCPMC8207177
OpenAlexW3167728079

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.