Evidence map›Paper›PMID 32341450›Full record

ArticleCell death and differentiation2020

Alpha synuclein aggregation drives ferroptosis: an interplay of iron, calcium and lipid peroxidation.

Plamena R Angelova, Minee L Choi, Alexey V Berezhnov, Mathew H Horrocks, Craig D Hughes, Suman De, Margarida Rodrigues, Ratsuda Yapom, Daniel Little, Karamjit S Dolt and 9 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 165 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
165citing papers in PubMed, 1 pooled it
19.0field-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

165 citing papers in PubMed, 1 synthesis or guideline pooled it, 289 citations in OpenAlex.

  1. Pooled it
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  12. Progress of Immunotherapies in Parkinson's Disease.CNS neuroscience & therapeutics · 2026
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105 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 11 institutions in 3 countries.

Plamena R Angelova *UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.ORCID http://orcid.org/0000-0003-4596-9117
Minee L Choi *UCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Alexey V BerezhnovInstitute of Cell Biophysics, Russian Academy of Sciences, Pushchino, 142290, Russia.
Mathew H HorrocksEaStCHEM School of Chemistry, University of Edinburgh, Edinburgh, UK.
Craig D HughesDepartment of Chemistry, University of Cambridge, Cambridge, UK.
Suman DeDepartment of Chemistry, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-1675-0773
Margarida RodriguesDepartment of Chemistry, University of Cambridge, Cambridge, UK.
Ratsuda YapomMRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, UK.
Daniel LittleMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, UK.
Karamjit S DoltMRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, UK.
Tilo KunathMRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-8805-7356
Michael J DevineMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, UK.ORCID http://orcid.org/0000-0001-6076-3382
Paul GissenMRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London, UK.ORCID http://orcid.org/0000-0002-9712-6122
Mikhail S ShchepinovRetrotope Inc., Los Altos, CA, 94022, USA.
Sergiy SylantyevUCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK.
Evgeny V PavlovCollege of Dentistry, New York University, New York, NY, USA.
David KlenermanDepartment of Chemistry, University of Cambridge, Cambridge, UK.
Andrey Y AbramovUCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK. a.abramov@ucl.ac.uk.
Sonia GandhiUCL Queen Square Institute of Neurology, Queen Square, London, WC1N 3BG, UK. sonia.gandhi@ucl.ac.uk.
University of Cambridge · GBMRC Centre for Regenerative Medicine · GBGreat Ormond Street Hospital · GBThe Francis Crick Institute · GBInstitute of Cell Biophysics · RUMRC Laboratory for Molecular Cell Biology · GBNational Hospital for Neurology and Neurosurgery · GBNew York University · USQueen Mary University of London · GBRetrotope (United States) · USUniversity of Aberdeen · GB

Funding

Department of HealthMedical Research Council MR/J012831/1Medical Research Council MR/T008199/1Parkinson's UK F-0902Wellcome TrustWellcome Trust WT089698
6 · The paper itself

Abstract

Protein aggregation and abnormal lipid homeostasis are both implicated in neurodegeneration through unknown mechanisms. Here we demonstrate that aggregate-membrane interaction is critical to induce a form of cell death called ferroptosis. Importantly, the aggregate-membrane interaction that drives ferroptosis depends both on the conformational structure of the aggregate, as well as the oxidation state of the lipid membrane. We generated human stem cell-derived models of synucleinopathy, characterized by the intracellular formation of α-synuclein aggregates that bind to membranes. In human iPSC-derived neurons with SNCA triplication, physiological concentrations of glutamate and dopamine induce abnormal calcium signaling owing to the incorporation of excess α-synuclein oligomers into membranes, leading to altered membrane conductance and abnormal calcium influx. α-synuclein oligomers further induce lipid peroxidation. Targeted inhibition of lipid peroxidation prevents the aggregate-membrane interaction, abolishes aberrant calcium fluxes, and restores physiological calcium signaling. Inhibition of lipid peroxidation, and reduction of iron-dependent accumulation of free radicals, further prevents oligomer-induced toxicity in human neurons. In summary, we report that peroxidation of polyunsaturated fatty acids underlies the incorporation of β-sheet-rich aggregates into the membranes, and that additionally induces neuronal death. This suggests a role for ferroptosis in Parkinson's disease, and highlights a new mechanism by which lipid peroxidation causes cell death.

Indexed as

FerroptosisLipid PeroxidationParkinson Diseasealpha-SynucleinCalciumCells, CulturedHuman Embryonic Stem CellsHumansInduced Pluripotent Stem CellsIronalpha-SynucleinCalciumIron

Identifiers

PMID32341450
PMCPMC7492459
OpenAlexW3018835152

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.