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Resources » Paper

Perni M et al. (2017) Proc Natl Acad Sci U S A "A natural product inhibits the initiation of -synuclein aggregation and suppresses its toxicity."

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  • Comments on Perni M et al. (2017) Proc Natl Acad Sci U S A "A natural product inhibits the initiation of -synuclein aggregation and suppresses its toxicity." (0)

  • Overview

    PMID:
    28096355
    DOI:
    10.1073/pnas.1610586114
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00050769

    Perni M, Galvagnion C, Maltsev A, Meisl G, Muller MB, Challa PK, Kirkegaard JB, Flagmeier P, Cohen SI, Cascella R, Chen SW, Limboker R, Sormanni P, Heller GT, Aprile FA, Cremades N, Cecchi C, Chiti F, Nollen EA, Knowles TP, Vendruscolo M, Bax A, Zasloff M, & Dobson CM (2017). A natural product inhibits the initiation of -synuclein aggregation and suppresses its toxicity. Proc Natl Acad Sci U S A. doi:10.1073/pnas.1610586114

    The self-assembly of -synuclein is closely associated with Parkinson's disease and related syndromes. We show that squalamine, a natural product with known anticancer and antiviral activity, dramatically affects -synuclein aggregation in vitro and in vivo. We elucidate the mechanism of action of squalamine by investigating its interaction with lipid vesicles, which are known to stimulate nucleation, and find that this compound displaces -synuclein from the surfaces of such vesicles, thereby blocking the first steps in its aggregation process. We also show that squalamine almost completely suppresses the toxicity of -synuclein oligomers in human neuroblastoma cells by inhibiting their interactions with lipid membranes. We further examine the effects of squalamine in a Caenorhabditis elegans strain overexpressing -synuclein, observing a dramatic reduction of -synuclein aggregation and an almost complete elimination of muscle paralysis. These findings suggest that squalamine could be a means of therapeutic intervention in Parkinson's disease and related conditions.

    Authors: Perni M, Galvagnion C, Maltsev A, Meisl G, Muller MB, Challa PK, Kirkegaard JB, Flagmeier P, Cohen SI, Cascella R, Chen SW, Limboker R, Sormanni P, Heller GT, Aprile FA, Cremades N, Cecchi C, Chiti F, Nollen EA, Knowles TP, Vendruscolo M, Bax A, Zasloff M, Dobson CM


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