The immune system of the central nervous system is distinct from that of the rest of the body, although there is a great deal of direct and indirect cross-talk between the two. The innate immune cells known as microglia are the central nervous system version of macrophages, and are involved in defense against pathogens, clearance of metabolic waste, and aspects of the normal function of brain tissue, such as maintenance of synaptic connections between neurons. With age, microglia become increasingly inflammatory, and many lines of evidence suggest that this behavior becomes maladaptive and is important in driving the onset and progression of neurodegenerative conditions. The research community is engaged in the search for ways to manipulate microglia into a better pattern of behavior, such as the example here.
Tim-3 is an immune checkpoint molecule involved in immunity and inflammation recently linked to late-onset Alzheimer's disease (AD), but its role in the brain was unknown until. Now researchers have used preclinical models to uncover Tim-3's role in microglia, the brain's resident immune cells, and have identified it as a promising therapeutic target for Alzheimer's disease. "Microglia are pivotal in neuroinflammation and neurodegeneration, and therapeutic targeting of Tim-3 in microglia may alter them to an optimal state to fight the disease pathology in AD."
Using a mouse model of AD, researchers determined that Tim-3 is only expressed in microglia in the central nervous system, where it helps the cells maintain a healthy state of homeostasis. Tim-3 can also, however, prevent the brain from effectively clearing out the toxic amyloid plaques that accumulate during AD. The researchers found that deleting Tim-3 helped kickstart plaque removal by prompting the microglia to eat up more of the plaques, while also producing anti-inflammatory proteins to reduce neuroinflammation, and limiting cognitive impairment.
Over a half-dozen clinical trials are currently testing therapeutics that target Tim-3 to treat patients with immunotherapy-resistant cancers. The new study highlights the therapeutic potential of adapting these treatments to enhance plaque clearance and mitigate neurodegeneration in Alzheimer's disease.
View the full article at FightAging
