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  • A Grand Challenge. 2. Phenotypic Profiling of a Natural Product Library on Parkinson's Patient-Derived Cells

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    Version of Record (VoR)
    Author(s)
    Vial, Marie-Laure
    Zencak, Dusan
    Grkovic, Tanja
    Gorse, Alain-Dominique
    Mackay-Sim, Alan
    Mellick, George D
    Wood, Stephen A
    Quinn, Ronald J
    Griffith University Author(s)
    Quinn, Ronald J.
    Mackay-Sim, Alan
    Mellick, George
    Vial, Marie-Laure
    Year published
    2016
    Metadata
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    Abstract
    Harnessing the inherent biological relevance of natural products requires a method for the recognition of biological effects that may subsequently lead to the discovery of particular targets. An unbiased multidimensional profiling method was used to examine the activities of natural products on primary cells derived from a Parkinson’s disease patient. The biological signature of 482 natural products was examined using multiparametric analysis to investigate known cellular pathways and organelles implicated in Parkinson’s disease such as mitochondria, lysosomes, endosomes, apoptosis, and autophagy. By targeting several cell ...
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    Harnessing the inherent biological relevance of natural products requires a method for the recognition of biological effects that may subsequently lead to the discovery of particular targets. An unbiased multidimensional profiling method was used to examine the activities of natural products on primary cells derived from a Parkinson’s disease patient. The biological signature of 482 natural products was examined using multiparametric analysis to investigate known cellular pathways and organelles implicated in Parkinson’s disease such as mitochondria, lysosomes, endosomes, apoptosis, and autophagy. By targeting several cell components simultaneously the chance of finding a phenotype was increased. The phenotypes were then clustered using an uncentered correlation. The multidimensional phenotypic screening showed that all natural products, in our screening set, were biologically relevant compounds as determined by an observed phenotypic effect. Multidimensional phenotypic screening can predict the cellular function and subcellular site of activity of new compounds, while the cluster analysis provides correlation with compounds with known mechanisms of action. This study reinforces the value of natural products as biologically relevant compounds.
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    Journal Title
    Journal of Natural Products
    Volume
    79
    Issue
    8
    DOI
    https://doi.org/10.1021/acs.jnatprod.6b00258
    Copyright Statement
    © 2016 The American Chemical Society and American Society of Pharmacognosy. This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
    Subject
    Chemical sciences
    Biological sciences
    Other biological sciences not elsewhere classified
    Biomedical and clinical sciences
    Publication URI
    http://hdl.handle.net/10072/100261
    Collection
    • Journal articles

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