Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Similar neuronal imprint and absence of cross-seeded partner fibrils in α-synuclein aggregates from MSA and Parkinson’s disease brains

View ORCID ProfileFlorent Laferrière, Stéphane Claverol, View ORCID ProfileErwan Bezard, Francesca De Giorgi, View ORCID ProfileFrançois Ichas
doi: https://doi.org/10.1101/2021.06.22.449410
Florent Laferrière
1CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
2Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Florent Laferrière
  • For correspondence: florent.laferriere@u-bordeaux.fr francois.ichas@inserm.fr
Stéphane Claverol
3Plateforme Proteome, Univ. Bordeaux, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erwan Bezard
1CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
2Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Erwan Bezard
Francesca De Giorgi
1CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
2Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
4INSERM, Laboratoire de Neurosciences Expérimentales et Cliniques, U-1084, Université de Poitiers, Poitiers, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
François Ichas
1CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
2Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France
4INSERM, Laboratoire de Neurosciences Expérimentales et Cliniques, U-1084, Université de Poitiers, Poitiers, France
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for François Ichas
  • For correspondence: florent.laferriere@u-bordeaux.fr francois.ichas@inserm.fr
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Aggregated alpha-synuclein (α-syn) is a principal constituent of Lewy bodies (LBs) and glial cytoplasmic inclusions (GCIs) observed respectively inside neurons in Parkinson’s disease (PD) and oligodendrocytes in multiple system atrophy (MSA). Yet, the cellular origin, the pathophysiological role, and the mechanism of formation of these inclusions bodies (IBs) remain to be elucidated. It has recently been proposed that α-syn IBs eventually cause the demise of the host cell by virtue of the cumulative sequestration of partner proteins and organelles. In particular, the hypothesis of a local cross-seeding of other fibrillization-prone proteins like tau or TDP-43 has also been put forward. We submitted sarkosyl-insoluble extracts of post-mortem brain tissue from PD, MSA and control subjects to a comparative proteomic analysis to address these points. Our studies indicate that: i) α-syn is by far the most enriched protein in PD and MSA extracts compared to controls; ii) PD and MSA extracts share a striking overlap of their sarkosyl-insoluble proteomes, consisting of a vast majority of mitochondrial and neuronal synaptic proteins, and (iii) other fibrillization-prone protein candidates possibly cross-seeded by α-syn are neither found in PD nor MSA extracts. Thus, our results (i) support the idea that pre-assembled building blocks originating in neurons serve to the formation of GCIs in MSA, (ii) show no sign of amyloid cross-seeding in either synucleinopathy, and (iii) point to the sequestration of mitochondria and of neuronal synaptic components in both LBs and GCIs.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵† Co-senior authorship.

  • ABBREVIATIONS

    α-syn
    Alpha-synuclein
    CTL
    Control
    PD
    Parkinson’s disease
    MSA
    Multiple system atrophy
    IB
    Inclusion body
    LB
    Lewy body
    GCI
    Glial cytoplasmic inclusion
    MS
    Mass spectrometry
    GO
    Gene ontology
    FC
    Fold change
  • Copyright 
    The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
    Back to top
    PreviousNext
    Posted June 22, 2021.
    Download PDF

    Supplementary Material

    Email

    Thank you for your interest in spreading the word about bioRxiv.

    NOTE: Your email address is requested solely to identify you as the sender of this article.

    Enter multiple addresses on separate lines or separate them with commas.
    Similar neuronal imprint and absence of cross-seeded partner fibrils in α-synuclein aggregates from MSA and Parkinson’s disease brains
    (Your Name) has forwarded a page to you from bioRxiv
    (Your Name) thought you would like to see this page from the bioRxiv website.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Share
    Similar neuronal imprint and absence of cross-seeded partner fibrils in α-synuclein aggregates from MSA and Parkinson’s disease brains
    Florent Laferrière, Stéphane Claverol, Erwan Bezard, Francesca De Giorgi, François Ichas
    bioRxiv 2021.06.22.449410; doi: https://doi.org/10.1101/2021.06.22.449410
    Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
    Citation Tools
    Similar neuronal imprint and absence of cross-seeded partner fibrils in α-synuclein aggregates from MSA and Parkinson’s disease brains
    Florent Laferrière, Stéphane Claverol, Erwan Bezard, Francesca De Giorgi, François Ichas
    bioRxiv 2021.06.22.449410; doi: https://doi.org/10.1101/2021.06.22.449410

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Subject Area

    • Neuroscience
    Subject Areas
    All Articles
    • Animal Behavior and Cognition (4087)
    • Biochemistry (8766)
    • Bioengineering (6480)
    • Bioinformatics (23346)
    • Biophysics (11751)
    • Cancer Biology (9150)
    • Cell Biology (13255)
    • Clinical Trials (138)
    • Developmental Biology (7417)
    • Ecology (11370)
    • Epidemiology (2066)
    • Evolutionary Biology (15088)
    • Genetics (10402)
    • Genomics (14012)
    • Immunology (9122)
    • Microbiology (22050)
    • Molecular Biology (8780)
    • Neuroscience (47375)
    • Paleontology (350)
    • Pathology (1420)
    • Pharmacology and Toxicology (2482)
    • Physiology (3704)
    • Plant Biology (8050)
    • Scientific Communication and Education (1431)
    • Synthetic Biology (2209)
    • Systems Biology (6016)
    • Zoology (1250)