title: A Grand Challenge. 2. Phenotypic Profiling of a Natural Product Library on Parkinson's Patient-Derived Cells.
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 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.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Vial
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Dusan
authors.initials: D
authors.lastname: Zencak
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Tanja
authors.initials: T
authors.lastname: Grkovic
authors.affiliation: QFAB Bioinformatics, Institute for Molecular Bioscience, The University of Queensland , St Lucia, QLD 4072, Australia.
authors.forename: Alain-Dominique
authors.initials: AD
authors.lastname: Gorse
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Alan
authors.initials: A
authors.lastname: Mackay-Sim
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: George D
authors.initials: GD
authors.lastname: Mellick
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Wood
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University , Brisbane, QLD 4111, Australia.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001688:Biological Products / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010300:Parkinson Disease; D054852:Small Molecule Libraries
chemical_list: D001688:Biological Products; D054852:Small Molecule Libraries