Unveiling the Culprit: Microglial Galectin-3 Aggravates Tauopathy
Dr. Yijuang Chern from Academia Sinica, with Dr. Jian Jing Siew as the lead author, published a significant study in the Journal of Clinical Investigation on November 21, 2023. Their research provides new insights into Alzheimer's disease and related brain conditions, known collectively as tauopathies. The study, titled 'Galectin-3 aggravates microglial activation and tau transmission in tauopathy', reveals the critical role of a protein called Galectin-3 in worsening these conditions. This protein is found in the brain's immune cells, called microglia, in both humans and mice suffering from tauopathies.
Galectin-3 is shown to exacerbate the condition by speeding up the accumulation of a harmful protein known as hyperphosphorylated tau (pTau), a hallmark of these diseases. Intriguingly, the presence of pTau stimulates the release of more Galectin-3 and tiny structures called extracellular vesicles from the microglia. These vesicles contain both Galectin-3 and pTau, further intensifying the disease's progression. The study also involved advanced genetic analysis at the single-cell level in a mouse model of tauopathy. It was found that microglia associated with Galectin-3 exhibit heightened immune and inflammatory responses, which are detrimental to the health of the brain. Crucially, removing Galectin-3 from mice with tauopathy led to significant improvements, including reduced microglia activation, decreased levels of the harmful pTau protein, and a noticeable enhancement in memory function.
This research, a joint effort with international teams from France and the USA, puts Galectin-3 in the spotlight as a potential target for developing new treatments for tauopathy and similar neurodegenerative diseases.
Article link (Journal of Clinical Investigation)