Microglial Metabolic Reprogramming in Alzheimer's Disease
Alzheimer’s disease (AD) is a devastating neurodegenerative condition that is considered to be the result of nerve cell defects in the brain. Abnormal behavior of microglia, the resident immune cells of the brain, has also been observed in AD. However, the cause of this abnormality and the role of microglia in AD remain elusive. Our studies in an animal model of AD have revealed a severe defect in energy metabolism in microglia, which causes these cells to become highly inflammatory. Remarkably, treatment of the animals with a compound that regulates energy metabolism in microglia corrects this abnormality and ameliorates disease. In our proposed project we will use cutting-edge technology to investigate how altered energy metabolism of microglia contributes to AD, and reformulate our energy-regulating compound for further preclinical development, and confirm the ability of the reformulated compound to correct the abnormality and ameliorate disease in animal models of AD.