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Updated: Aug 19, 2025

Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
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Castor1 overexpression regulates microglia M1/M2 polarization via inhibiting mTOR pathway

Huiling Hu1,2, Xiaoxia Lu3,4, Lisi Huang3,4

  • 1Department of Clinical Laboratory, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. huhling5@mail.sysu.edu.cn.

Metabolic Brain Disease
|December 1, 2022
PubMed

Insights

Castor1 regulates microglial polarization by inhibiting the mammalian target of rapamycin (mTOR) pathway. This finding suggests the Castor1-mTOR pathway as a potential therapeutic target for central nervous system diseases.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglia, the brain's immune cells, are implicated in neuroinflammation and neurodegenerative diseases.
  • The mammalian target of rapamycin (mTOR) pathway is crucial for microglial polarization.
  • Castor1, an arginine sensor for mTOR complex 1 (mTORC1), has an unknown role in microglial polarization.

Purpose of the Study:

  • To investigate the regulatory effect of Castor1 on microglial polarization.
  • To elucidate the underlying molecular mechanisms of Castor1's action.
  • To explore the potential of the Castor1-mTOR pathway as a therapeutic target.

Main Methods:

  • Assessed Castor1 expression in microglia treated with lipopolysaccharides (LPS) and interferon-gamma (IFN-γ).
  • Investigated the impact of Castor1 overexpression on M1 and M2 microglial polarization markers.
  • Examined the effect of Castor1 on mTOR signaling pathway activation.
  • Utilized an mTOR activator (MHY1485) to confirm the mechanism of action.

Main Results:

  • Castor1 expression decreased in LPS/IFN-γ treated microglia.
  • Castor1 overexpression inhibited M1 polarization and promoted M2 polarization.
  • Castor1 overexpression suppressed mTOR signaling pathway activation.
  • The inhibitory effect of Castor1 on M1 polarization was dependent on mTOR pathway inhibition.

Conclusions:

  • Castor1 negatively regulates M1 microglial polarization and promotes M2 polarization.
  • The Castor1-mTOR signaling pathway is a key regulator of microglial polarization.
  • Targeting the Castor1-mTOR pathway offers a potential therapeutic strategy for central nervous system diseases.
Keywords:
Castor1M1/M2 phenotypeMicrogliaPolarizationmTOR signaling pathway

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