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 Jiou Wang, MD, PhD, 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 - Americans - Time - Degeneration - Neurons
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.
Researchers first linked inherited FUS mutations to subsets of ALS and FTD cases in 2009. Since then, studies have found that even when it is not mutated, the protein often exists in abnormal clumps outside the cell nucleus where it normally works. That suggests its disruption is a common event in the disease process.
FUS - Cells - Clues - ALS - FTD
Knowing what FUS normally does in cells should provide clues to how ALS and FTD originate. FUS is an RNA- and DNA-binding protein and works...
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