Photo credit: www.sciencedaily.com
Tim-3, an immune checkpoint molecule associated with immune responses and inflammation, has recently been linked to late-onset Alzheimer’s disease (AD). However, prior to recent research, its specific functions within the brain were largely unknown. A study published in Nature by researchers from Mass General Brigham sheds light on Tim-3’s role in microglia— the immune cells native to the central nervous system— and identifies it as a promising target for therapeutic intervention in Alzheimer’s disease.
“The emergence of immune checkpoint inhibitors has significantly transformed cancer treatment, and we are hopeful that these strategies can be adapted for Alzheimer’s disease,” remarked senior author Vijay Kuchroo, PhD, DVM, from the Gene Lay Institute of Immunology and Inflammation at Brigham and Women’s Hospital and Massachusetts General Hospital, both integral parts of the Mass General Brigham healthcare system. “Given the critical function of microglia in neuroinflammation and neurodegeneration, specifically targeting Tim-3 could potentially reprogram these cells to effectively address the pathological processes seen in AD.”
Employing a mouse model of Alzheimer’s, the Kuchroo lab, in collaboration with Oleg Butovsky’s lab from the Ann Romney Center for Neurologic Diseases at BWH, established that Tim-3’s expression is exclusive to microglia within the central nervous system. This molecule plays a crucial role in maintaining microglial homeostasis. However, it also inhibits the brain’s ability to effectively clear the toxic plaques that characterize Alzheimer’s disease. Their findings indicated that the elimination of Tim-3 significantly enhances plaque clearance, as the microglia increased their phagocytic activity towards the plaques, while concurrently producing anti-inflammatory proteins that alleviate neuroinflammation and support cognitive function.
Currently, over six clinical trials are being conducted to evaluate therapeutics targeting Tim-3 for patients suffering from cancers resistant to traditional immunotherapy. The insights from this new study suggest that there may be valuable applications for these treatments in promoting plaque degradation and reducing neurodegenerative effects in Alzheimer’s disease.
Source
www.sciencedaily.com