Galectin-3, a rising star in modulating microglia activation under conditions of neurodegeneration

The advent of high-throughput single-cell transcriptomic analysis of microglia has revealed different phenotypes that are inherently associated with disease conditions. A common feature of some of these activated phenotypes is the upregulation of galectin-3. Representative examples of these phenotypes include disease-associated microglia (DAM) and white-associated microglia (WAM), whose role(s) in neuroprotection/neurotoxicity is a matter of high interest in the microglia community. In this review, we summarise the main findings that demonstrate the ability of galectin-3 to interact with key pattern recognition receptors, including, among others, TLR4 and TREM2 and the importance of galectin-3 in the regulation of microglia activation. Finally, we discuss increasing evidence supporting the involvement of this lectin in the main neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, and stroke.
We thank the Spanish Ministerio de Ciencia, Innovación y Universidades/FEDER/UE RTI2018-098645-B-100, PID2019-107948RA-I00 and RYC-2017-21804; the Agencia Española de Investigación PID2021-124096OB-I00 and PID2021-126090OA-I00; the Spanish Junta de Andalucia /FEDER/EU P18-RT-1372 and the Spanish FEDER I + D + i-USE US-1264806, US-1264152 and US-1265062 from University of Seville. This work has also been supported by the Strategic Research Area MultiPark (Multidisciplinary Research focused on neurodegenerative diseases) at Lund University, the Swedish Alzheimer foundation, the Swedish Brain Foundation, the Crafoord Foundation, the Swedish Dementia Association, the G&J Kock Foundation, the Olle Engkvist Foundation, the Swedish Research Council (Project 2019-06333), the Royal Physiographic Society (42222 and 40594), the A.E. Berger Foundation, the Swedish Parkinson Foundation and the Medical Faculty at Lund University. Open access funding provided by Lund University.