Beyond neurons: dissecting sacsin-related mechanisms underlying oligodendrocyte dysfunction in ARSACS

Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) is a rare inherited brain disorder that causes muscle stiffness, poor coordination, and progressive loss of motor control. It is caused by mutations in a gene making a protein called sacsin, crucial for brain cell health. Until recently, research focused mainly on nerve cells affected in the disease. However, new discoveries show a type of brain cell called oligodendrocytes also produce sacsin. Oligodendrocytes are vital for neuronal healthy because they wrap nerve fibers in myelin, a protective coating essential for nerve signal transmission and brain function. Our project will use cutting-edge tools to study how loss of sacsin affects these supporting cells and their ability to make myelin. We will examine human oligodendrocytes engineered to lack sacsin to understand its role in myelin formation and cell function. This knowledge aims to uncover new ways to protect both nerve and support cells in ARSACS, ultimately contributing to developing better treatments for patients living with this disabling disease.