Northwestern Medicine Study Uncovers Critical Molecular Mechanism Underlying Amyotrophic Lateral Sclerosis (ALS)

A Northwestern Medicine study has shed light on a critical molecular mechanism underlying amyotrophic lateral sclerosis (ALS), according to findingspublishedin the journalNeuron. The research points to a failure in the cell's RNA "quality control" system, which normally keeps genetic messages clean and functional. Every cell uses RNA as a messenger to carry instructions from DNA to make proteins, but these messages can sometimes be faulty or incomplete in ALS patients, said Evangelos Kiskinis, Ph.D., associate professor in the Ken and Ruth Davee Department of Neurology's Division of Neuromuscular Disease and of Neuroscience, who was senior author of the study. "In most ALS patients, we know that a predominantly nuclear RNA-binding protein known as TDP-43 leaves the nucleus and forms cytoplasmic aggregates," Kiskinis said. "This mislocalization of TDP-43 underlies the pathophysiology of the disease. In this study, we focused on understanding how loss-of-function of TDP-43 in human motor neurons affects RNA metabolism."