Grant: Project Grant

Multiple sclerosis (MS) is a brain disease where immune cells like T-cells and B-cells mistakenly attack the protective covering (myelin) of neurons, the specialized cells that send information throughout the body for its proper functioning. Oligodendrocytes, responsible for producing and wrapping myelin around neurons, also become target of this immune attack. A set of immune cells called macrophages that enter the brain during MS, and microglia, which are brain residing macrophages, remove the damaged myelin, which is important for the addition of new myelin layers by oligodendrocytes. However, if macrophages and microglia remain active for an extended period, they release substances that cause prolonged inflammation, leading to tissue damage. This results in the death of neurons which causes disability. Our research has discovered that macrophages depend on glucose, a type of sugar, through a process known as glycolysis as their main energy source when they enter the brains of people with MS and in a mouse model of MS called experimental autoimmune encephalomyelitis (EAE). When we lowered the levels of a key protein called extracellular matrix metalloproteinase inducer (EMMPRIN), which supports glycolysis in macrophages, these cells lost their ability to cause inflammation. However, we do not fully understand if glycolysis and associated pathways within macrophages and microglia cause MS progression. Therefore, we are investigating the energy needs of macrophages and microglia over an extended period during EAE and in samples obtained from the brains of individuals with progressive MS. Our aim is to identify and test drug targets that can effectively reduce the disease-causing activities of macrophages and microglia in progressive MS, providing hope for better outcomes for individuals with MS.