Polypeptides derived from [alpha]-Synuclein binding partners to prevent [alpha]-Synuclein fibrils interaction with and take-up by cells

[alpha]-Synuclein ([alpha]Syn) fibrils spread from one neuronal cell to another. This prion-like phenomenon is believed to contribute to the progression of the pathology in Parkinson's disease and other synucleinopathies. The binding of [alpha]Syn fibrils originating from affected cells to the...

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Bibliographic Details
Published in:PloS one 2020-08, Vol.15 (8), p.e0237328
Main Authors: Monsellier, Elodie, Bendifallah, Maya, Redeker, Virginie, Melki, Ronald
Format: Article
Language:English
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Summary:[alpha]-Synuclein ([alpha]Syn) fibrils spread from one neuronal cell to another. This prion-like phenomenon is believed to contribute to the progression of the pathology in Parkinson's disease and other synucleinopathies. The binding of [alpha]Syn fibrils originating from affected cells to the plasma membrane of naïve cells is key in their prion-like propagation propensity. To interfere with this process, we designed polypeptides derived from proteins we previously showed to interact with [alpha]Syn fibrils, namely the molecular chaperone Hsc70 and the sodium/potassium pump NaK-ATPase and assessed their capacity to bind [alpha]Syn fibrils and/or interfere with their take-up by cells of neuronal origin. We demonstrate here that polypeptides that coat [alpha]Syn fibrils surfaces in such a way that they are changed affect [alpha]Syn fibrils binding to the plasma membrane components and/or their take-up by cells. Altogether our observations suggest that the rationale design of [alpha]Syn fibrils polypeptide binders that interfere with their propagation between neuronal cells holds therapeutic potential.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0237328