Galectins in the brain: advances in neuroinflammation, neuroprotection and therapeutic opportunities.

PURPOSE OF REVIEW

Galectin interactions with glycoproteins and glycolipids modulate a variety of cellular responses that are now increasingly explored to better understand neuroinflammation processes and eventually find new therapeutic opportunities for neurological diseases.

RECENT FINDINGS

Gal-1 confirmed its indirect neuroprotective roles through anti-inflammatory properties whereas Gal-3 remains elusive, showing anti-inflammatory or pro-inflammatory roles depending on damaging conditions and genetic background of mice models. Interestingly, microglial intracellular rather than extracellular overexpression of Gal-3 arose as contributing to the pathogenesis of Huntington disease, involving NLRP3 inflammasome activation and inhibition of autophagic removal of damaged endolysosomes. Decreasing Gal-3 expression had favorable effects upon disease symptoms. Gal-3 expanded its role in this endolysosomal surveillance system originally involving Gal-8 and Gal-9, which protect cells against neuropathogenic proteins and becomes impaired or even detrimental under neurodegenerative conditions. Also, Gal-1, Gal-3 and Gal-4, together with changes in glycan structures define the outcome of neuroinflammation and remyelination processes. Gal-8 emerged as a new neuroprotector factor, which added to its immunosuppressive role and presence in human cerebrospinal fluid (CSF) may generate a neuroprotective environment in the brain.

SUMMARY

Galectins modulate neuroinflammation and neurodegenerative processes contributing to microglia polarization, immunosurveillance and neuroprotection through extracellular and intracellular interactions with particular and dynamic patterns of glycans, suggesting potential therapeutic targets.