The protein FUS, whose mutation or disruption causes many cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), works as a central component of one of the most important regulatory systems in cells, according to a new study in Molecular Cell from scientists at Johns Hopkins Bloomberg School of Public Health.
Precisely what FUS does in cells and why its dysfunction causes the deaths of neurons in ALS and FTD has long been a mystery. The scientists found evidence, though, that FUS is a key part of a system called the microRNA-mediated gene silencing system, which fine-tunes cellular activity by blocking the translation of certain genes into proteins.
“Thousands of microRNAs work in cells as part of this system, so our findings suggest that the disruption of FUS could lead to widespread failures of normal gene-expression regulation, which in turn could contribute to the development of these neurodegenerative diseases,” says study senior author Dr. Jiou Wang, associate professor in the Bloomberg School’s department of biochemistry and molecular biology. “Knowing how these diseases arise should of course be helpful in devising strategies to treat them.”
ALS, which affects about 30,000 Americans at any one time, features the degeneration of muscle-controlling neurons in the brain and the spinal cord, ultimately leading to respiratory failure. Most patients die within a few years of the first appearance of symptoms. FTD is the second most common dementia after Alzheimer’s disease in people younger than 65, and primarily involves the degeneration of frontal and temporal lobe neurons, with associated disruptions to cognitive and executive functions. It progresses to profound dementia and immobility and usually is fatal within a decade of diagnosis.