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The atypical RhoGTPase RhoE/Rnd3 is a key molecule to acquire a neuroprotective phenotype in microglia

Veronika E Neubrand1, Irene Forte-Lago2, Marta Caro2

  • 1Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Avd. Conocimiento 17, PTS Granada, 18016, Granada, Spain. veronika.neubrand@gmail.com.

Journal of Neuroinflammation
|December 17, 2018
PubMed
Abstract

Insights

Researchers identified key molecules, including RhoE/Rnd3, that help switch microglia from a harmful to a protective state, potentially aiding neurodegenerative disease treatment.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Immunology

Background:

  • Over-activated microglia contribute to neuroinflammation, neuronal death, and neurodegeneration.
  • Shifting microglia to a neuroprotective phenotype could restore a healthy central nervous system environment.
  • Identifying molecules that regulate this phenotypic transition is crucial for therapeutic development.

Purpose of the Study:

  • To identify intracellular molecules involved in the transition of primary microglia to a ramified, neuroprotective phenotype.
  • To leverage conditioned medium from adipose-derived mesenchymal stem cells (CM) to induce this neuroprotective phenotype in vitro.

Main Methods:

  • A microscopy-based siRNA screen was employed to identify genes regulating microglial phenotype.
  • 157 siRNAs targeting cytoskeleton and activation/inflammatory pathway genes were initially screened.
  • Hits were validated through individual siRNA assays and protein expression analysis, followed by functional screening.

Main Results:

  • 45 siRNAs inhibited, while 50 promoted, the CM-induced transition to a neuroprotective microglia phenotype.
  • Validation confirmed seven key targets, identifying RhoE/Rnd3 as essential for BDNF expression and microglial migration.
  • RhoE/Rnd3 was identified as a novel inducer of a potential neuroprotective microglia phenotype.

Conclusions:

  • RhoE/Rnd3 is a novel factor that can induce a neuroprotective microglia phenotype.
  • The study provides a list of potential therapeutic targets for further investigation.
  • Targeted modulation of these molecules may offer strategies for treating neurodegenerative conditions.
Keywords:
Cell morphologyMicrogliaNeuroinflammationsiRNA screen

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