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Galectins may act as danger\u2010associated molecular patterns in innate immunity and\/or as pattern\u2010recognition receptors that bind to pathogen\u2010associated molecular patterns. Among different galectin family members, galectin\u20103 has been the focus of studies in neurodegenerative diseases in recent years. This lectin modulates brain innate immune responses, microglia activation patterns in physiological and pathophysiological settings in a context\u2010dependent manner. Galectin\u20103 is considered as a pivotal tuner of macrophage and microglial activity. Indeed galectin\u20103 acts as a double edged sword in neuroinflammatory context and this multimodal lectin has diverse roles in physiological and pathophysiological conditions. Better understanding of galectin\u20103 physiology (its extracellular and intracellular actions) and structure (its C terminus vs. N terminus) is instrumental to design molecules that selectively modulate galectin\u20103 function toward neuroprotective phenotypes. Several experimental studies using different approaches and methods have demonstrated both protective and deleterious effects of galectin\u20103 in neuroinflammatory diseases. According to the crucial role of galectin\u20103 in modulation of innate immune response in brain, it is an attractive target in drug discovery of neurodegenerative diseases. The current insight attempts to provide an updated and balanced discussion on the role of galectin\u20103 as a complex endogenous immune modulator. This helps to have a better insight into the development of galectin\u20103 modulators with translational value in different neurological disorders including stroke and neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease and Parkinson's disease.<\/jats:p>","DOI":"10.1002\/med.21784","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T04:45:44Z","timestamp":1616042744000},"page":"2582-2589","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Microglia\u2010derived galectin\u20103 in neuroinflammation; a bittersweet ligand?"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3509-0400","authenticated-orcid":false,"given":"Reza","family":"Rahimian","sequence":"first","affiliation":[{"name":"McGill Group for Suicide Studies McGill University  Montreal Quebec 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