Explanation for Protein Clumps in Autopsy of ALS Patients

Researchers from Johns Hopkins University recently reported in the journal Science that they have discovered why the abnormal accumulation of proteins occur in the brains of patients with the neurodegenerative disorder amyotropic lateral sclerosis (ALS), in addition to those with frontotemporal dementia (FTD), based on analyzing how those same proteins function normally. Prior to this research, scientists didn’t know the precise role of TDP-43, which is normally responsible for keeping unwanted stretches of RNA from being used by nerve cells to create proteins. When TDP-43 bunches up inside those cells, it malfunctions, lifting the brakes on cryptic exons and causing a cascade of events that kills brain or spinal cord cells. When the researchers studied brain autopsies from patients with ALS and FTD, they confirmed that not only were there buildups of TDP-43, but also cryptic exons in the degenerated brain cells. In the brains of healthy people, however, they saw no cryptic exons. This finding, the researchers say, suggests that when TDP-43 is clumped together, it no longer works, causing cells to function abnormally as though there’s no TDP-43 at all. To read more about this study, click here.