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Abstract

Microglia serve as the brain's immune guardians. Overactivation of microglia is closely linked to neurodegeneration. Galectin-3 (Gal3), a protein that binds with β-galactoside, has been extensively studied in numerous peripheral system diseases, including lung scarring, various cancers, and heart and kidney failures. Recently, due to its elevated levels in activated microglia, Gal3 has garnered significant attention in the field of neuroscience. In this presentation, I will discuss how human iPSC-derived microglia-like cells respond to exposure to the pathogenic tau protein—a key factor in neurodegeneration—and how they contribute to the spread of this harmful tau protein in the brain via a Gal3-dependent pathway. Considering the connection between microglial activation and various brain disorders, our insights into Gal3's pathogenic role could deepen our understanding of microglial reactions to misfolded proteins. This knowledge can further guide the development of treatments that target Gal3 in neurodegenerative diseases, such as Huntington’s and Alzheimer's, which are characterized by the accumulation of misfolded proteins that cause disease and inflammation driven by microglia.

References: 

1. Siew JJ, Chen H-M, Chen H-Y, Chen H-L, Chen C-M, Soong B-W, Wu Yih-Ru, Chang C-P, Chan Y-C, Lin C-H, Liu F-T and Chern Y^ξ (2019) Galectin-3 is required for the microglia-mediated brain inflammation in Huntington’s disease. Nature Communications 10, 3473-3490.
2. Siew JJ, Chern Y, Khoo K-H, Angata T^ξ (2023) Roles of Siglecs in neurodegenerative diseases. Molecular Aspects of Medicine 90:101141.
3. Siew JJ, Chen H-M, Chiu F-L, Lee C-W, Chang Y-M, Chen H-L, Nguyen TNA, Liao H-T, Liu M, Hagar H-T, Sun Y-C, Lai H-L, Kuo M-H, Blum D, Buee L, Jin L-W, Chen S-Y, Ko T-M, Huang J-r, Kuo H-C, Liu F-T, Chern Y^ξ (2023) Galectin-3 aggravates microglial activation and tau transmission in tauopathy. Journal of Clinical Investigation doi: 10.1172/JCI165523.