Galectin-3 alleviates demyelination by modulating microglial anti-inflammatory polarization through PPARγ-CD36 axis

Area of Science:

• Neuroscience
• Immunology
• Cell Biology

Background:

• Demyelination disrupts the myelin sheath, impacting neurological function, with limited therapeutic options.
• Microglia, particularly those with an anti-inflammatory phenotype, are essential for effective remyelination.
• Galectin-3 (Gal-3) influences microglial activation and is linked to myelination processes.

Purpose of the Study:

• To investigate the role of Gal-3 in myelin formation and remyelination.
• To evaluate the therapeutic potential and underlying mechanisms of recombinant Gal-3 (rGal-3) in promoting remyelination.

Main Methods:

• Utilized Gal-3 knockout (Lgals3 KO) mice to study demyelination during spontaneous myelinogenesis.
• Employed a cuprizone (CPZ)-induced demyelination model to assess the effects of Gal-3 deficiency and rGal-3 administration.
• Conducted RNA sequencing and pharmacological inhibition (SSO, GW9662) to explore the PPARγ-CD36 axis.

Main Results:

• Lgals3 KO mice exhibited demyelination and exacerbated lesions in the CPZ model, with a shift towards pro-inflammatory microglia.
• rGal-3 administration ameliorated CPZ-induced demyelination and promoted an anti-inflammatory microglial phenotype.
• Gal-3's effects on microglial polarization were mediated through the regulation of the PPARγ-CD36 signaling pathway.

Conclusions:

• Gal-3 plays a vital role in endogenous myelination and remyelination processes.
• rGal-3 administration represents a promising therapeutic strategy for demyelinating diseases by modulating microglial polarization.
• Targeting the Gal-3-mediated PPARγ-CD36 axis offers a novel approach for enhancing remyelination therapies.