biostudies-literatureNeubrand VEMichael J. Fox Foundation for Parkinson's ResearchExcellence Grant of the Andalusian GovernmentMichael J. Fox Foundation for Parkinson&apos;s Research343https://www.ebi.ac.uk/biostudies/studies/S-EPMC6295018biostudies-literatureUnknown15(1)<h4>Background</h4>Over-activated microglia play a central role during neuroinflammation, leading to neuronal cell death and neurodegeneration. Reversion of over-activated to neuroprotective microglia phenotype could regenerate a healthy CNS-supporting microglia environment. Our aim was to identify a dataset of intracellular molecules in primary microglia that play a role in the transition of microglia to a ramified, neuroprotective phenotype.<h4>Methods</h4>We exploited the anti-inflammatory and neuroprotective properties of conditioned medium of adipose-derived mesenchymal stem cells (CM) as a tool to generate the neuroprotective phenotype of microglia in vitro, and we set up a microscopy-based siRNA screen to identify its hits by cell morphology.<h4>Results</h4>We initially assayed an aJournal of neuroinflammationThe atypical RhoGTPase RhoE/Rnd3 is a key molecule to acquire a neuroprotective phenotype in microglia.PMC6295018CTS 2939Grant ID 9404Forte-Lago IDelgado MCaro MNeubrand VEfalseThe atypical RhoGTPase RhoE/Rnd3 is a key molecule to acquire a neuroprotective phenotype in microglia.<h4>Background</h4>Over-activated microglia play a central role during neuroinflammation, leading to neuronal cell death and neurodegeneration. Reversion of over-activated to neuroprotective microglia phenotype could regenerate a healthy CNS-supporting microglia environment. Our aim was to identify a dataset of intracellular molecules in primary microglia that play a role in the transition of microglia to a ramified, neuroprotective phenotype.<h4>Methods</h4>We exploited the anti-inflammatory and neuroprotective properties of conditioned medium of adipose-derived mesenchymal stem cells (CM) as a tool to generate the neuroprotective phenotype of microglia in vitro, and we set up a microscopy-based siRNA screen to identify its hits by cell morphology.<h4>Results</h4>We initially assayed an a2018-01-01T00:00:00Z2018 Dec2026-07-13T03:11:48.898Z2019-03-27T00:12:31ZS-EPMC62950183055327010.1186/s12974-018-1386-z