Interactions between SARS-CoV-2 N-protein and α-synuclein accelerate amyloid formation

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Abstract

First cases that point at a correlation between SARS-CoV-2 infections and the development of Parkinson’s disease have been reported. Currently it is unclear if there also is a direct causal link between these diseases. To obtain first insights into a possible molecular relation between viral infections and the aggregation of α-synuclein protein into amyloid fibrils characteristic for Parkinson’s disease, we investigated the effect of the presence of SARS-CoV-2 proteins on α-synuclein aggregation. We show, in test tube experiments, that SARS-CoV-2 S-protein has no effect on α-synuclein aggregation while SARS-CoV-2 N-protein considerably speeds up the aggregation process. We observe the formation of multi-protein complexes, and eventually amyloid fibrils. Microinjection of N-protein in SHSY-5Y cells disturbed the α-synuclein proteostasis and increased cell death. Our results point toward direct interactions between the N-protein of SARS-CoV-2 and α-synuclein as molecular basis for the observed coincidence between SARS-CoV-2 infections and Parkinsonism.

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  1. SciScore for 10.1101/2021.04.12.439549: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cell culture, microinjection, and nuclear counterstaining: SH-SY5Y cells (ATCC, USA) were grown in proliferation medium (DMEM-F12 GlutaMAX™ + 10% heat inactivated FBS + 1% non-essential amino acids +10 mM HEPES buffer + 1% Penicillin/Streptomycin; Gibco®, Invitrogen, USA).
    SH-SY5Y
    suggested: None
    Software and Algorithms
    SentencesResources
    AFM images were processed with the Scanning Probe Image Processor (SPIP
    SPIP
    suggested: (SPIP, RRID:SCR_009410)
    Fibril morphology was analyzed using a custom fibril analysis Matlab script adapted from the FiberApp package.
    Matlab
    suggested: (MATLAB, RRID:SCR_001622)
    FiberApp
    suggested: (FiberApp, RRID:SCR_015826)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).


    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    Results from JetFighter: We did not find any issues relating to colormaps.


    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • No funding statement was detected.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.