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dc.contributor.authorWimalasena, Nivanthika K.
dc.contributor.authorLe, Viet Q.
dc.contributor.authorWimalasena, Kandatege
dc.contributor.authorSchreiber, Stuart L.
dc.contributor.authorKarmacharya, Rakesh
dc.identifier.citationGene Expression-Based Screen for Parkinson’s Disease Identifies GW8510 as a Neuroprotective Agent Nivanthika K. Wimalasena, Viet Q. Le, Kandatege Wimalasena, Stuart L. Schreiber, and Rakesh Karmacharya ACS Chemical Neuroscience 2016 7 (7), 857-863en_US
dc.descriptionClick on the DOI link to access the article (may not be free).en_US
dc.description.abstractWe carried out a gene expression-based in silico screen in order to identify small molecules with gene-expression profiles that are anticorrelated with a gene-expression profile for Parkinson's disease (PD). We identified the cyclin-dependent kinase 2/5 (CDK2/5) inhibitor GW8510 as our most significant hit and characterized its effects in rodent MN9D cells and in human neuronal cells derived from induced pluripotent stem cells. GW8510 demonstrated neuroprotective ability in MN9D cells in the presence of 1-methyl-4-phenylpyridium (MPP+), a widely used neurotoxin model for Parkinson's disease. In order to delineate the nature and extent of GW8510's neuroprotective properties, we studied GW8510 in human neuronal cells in the context of various mechanisms of cellular stress. We found that GW8510 was protective against small-molecule mitochondrial and endoplasmic reticulum stressors. Our findings illustrate an approach to using small-molecule gene expression libraries to identify compounds with therapeutic potential in human diseases.en_US
dc.description.sponsorshipNational Institute of Mental Health Award MH086846 (to RK.), by Steve Willis and Elissa Freud (to RK.), and by the National Institute of General Medical Sciences Award GM038627 (to S.L.S.).en_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofseriesACS Chemical Neuroscience;v.7:no.7
dc.subjectParkinson's diseaseen_US
dc.subjectInduced pluripotent stem cellsen_US
dc.subjectNeural progenitor cellsen_US
dc.titleGene expression-based screen for Parkinson's disease identifies GW8510 as a neuroprotective agenten_US
dc.rights.holderCopyright © 2016 American Chemical Societyen_US

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