Unravelling Neuromuscular Junction Resistance in ALS

Many researchers believe that one of the earliest events in ALS is the detachment of motor neurons from muscles at a site called the neuromuscular junction (NMJ) and have discovered that some NMJs are more vulnerable than others. In both humans and ALS laboratory mice, the eye muscles preserve the connections longer, which is why many assistive technology devices for ALS use eye movements for control. Previous work by Dr. Robitaille has revealed that specialized supporting cells called Perisynaptic Schwann Cells (PSCs) are critical for maintaining the NMJ connection and that PSC function is impaired in ALS mice. In this project, Dr. Robitaille will examine PSC function in ALS mice before and after they develop disease symptoms and compare the results to normal mice. He will also compare PSC function in eye NMJs with PSC function in leg NMJs, which are known to show early impairment. Also, Dr. Robitaille will analyze the entire set of proteins in both the resistant and susceptible NMJs and compare the results to look for specific markers that might explain the preserved function in eye muscles. If successful, this project could discover new targets for treatments that might preserve NMJs all over the body by enhancing PSC function.