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Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19

Author

Listed:
  • Mirren Charnley

    (Swinburne University of Technology
    Peter MacCallum Cancer Centre)

  • Saba Islam

    (La Trobe Institute for Molecular Science, La Trobe University)

  • Guneet K. Bindra

    (La Trobe Institute for Molecular Science, La Trobe University)

  • Jeremy Engwirda

    (La Trobe Institute for Molecular Science, La Trobe University)

  • Julian Ratcliffe

    (La Trobe University Bioimaging Platform)

  • Jiangtao Zhou

    (ETH Zurich)

  • Raffaele Mezzenga

    (ETH Zurich)

  • Mark D. Hulett

    (La Trobe Institute for Molecular Science, La Trobe University)

  • Kyunghoon Han

    (University of Luxembourg)

  • Joshua T. Berryman

    (University of Luxembourg)

  • Nicholas P. Reynolds

    (La Trobe Institute for Molecular Science, La Trobe University)

Abstract

COVID-19 is primarily known as a respiratory disease caused by SARS-CoV-2. However, neurological symptoms such as memory loss, sensory confusion, severe headaches, and even stroke are reported in up to 30% of cases and can persist even after the infection is over (long COVID). These neurological symptoms are thought to be produced by the virus infecting the central nervous system, however we don’t understand the molecular mechanisms triggering them. The neurological effects of COVID-19 share similarities to neurodegenerative diseases in which the presence of cytotoxic aggregated amyloid protein or peptides is a common feature. Following the hypothesis that some neurological symptoms of COVID-19 may also follow an amyloid etiology we identified two peptides from the SARS-CoV-2 proteome that self-assemble into amyloid assemblies. Furthermore, these amyloids were shown to be highly toxic to neuronal cells. We suggest that cytotoxic aggregates of SARS-CoV-2 proteins may trigger neurological symptoms in COVID-19.

Suggested Citation

  • Mirren Charnley & Saba Islam & Guneet K. Bindra & Jeremy Engwirda & Julian Ratcliffe & Jiangtao Zhou & Raffaele Mezzenga & Mark D. Hulett & Kyunghoon Han & Joshua T. Berryman & Nicholas P. Reynolds, 2022. "Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30932-1
    DOI: 10.1038/s41467-022-30932-1
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    References listed on IDEAS

    as
    1. Nicholas P. Reynolds & Jozef Adamcik & Joshua T. Berryman & Stephan Handschin & Ali Asghar Hakami Zanjani & Wen Li & Kun Liu & Afang Zhang & Raffaele Mezzenga, 2017. "Competition between crystal and fibril formation in molecular mutations of amyloidogenic peptides," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
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    4. Andrew C. Yang & Fabian Kern & Patricia M. Losada & Maayan R. Agam & Christina A. Maat & Georges P. Schmartz & Tobias Fehlmann & Julian A. Stein & Nicholas Schaum & Davis P. Lee & Kruti Calcuttawala &, 2021. "Dysregulation of brain and choroid plexus cell types in severe COVID-19," Nature, Nature, vol. 595(7868), pages 565-571, July.
    5. Andrew C. Yang & Fabian Kern & Patricia M. Losada & Maayan R. Agam & Christina A. Maat & Georges P. Schmartz & Tobias Fehlmann & Julian A. Stein & Nicholas Schaum & Davis P. Lee & Kruti Calcuttawala &, 2021. "Publisher Correction: Dysregulation of brain and choroid plexus cell types in severe COVID-19," Nature, Nature, vol. 598(7882), pages 4-4, October.
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    Cited by:

    1. Taniya Bhardwaj & Kundlik Gadhave & Shivani K. Kapuganti & Prateek Kumar & Zacharias Faidon Brotzakis & Kumar Udit Saumya & Namyashree Nayak & Ankur Kumar & Richa Joshi & Bodhidipra Mukherjee & Aparna, 2023. "Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Einav Tayeb-Fligelman & Jeannette T. Bowler & Christen E. Tai & Michael R. Sawaya & Yi Xiao Jiang & Gustavo Garcia & Sarah L. Griner & Xinyi Cheng & Lukasz Salwinski & Liisa Lutter & Paul M. Seidler &, 2023. "Low complexity domains of the nucleocapsid protein of SARS-CoV-2 form amyloid fibrils," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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