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Researchers studying amyotrophic lateral sclerosis, or ALS, have long been suspicious about the protein known as TDP-43. Now, in a publication in Nature Neuroscience, Mayo researchers provide enough evidence to indict the protein as an ALS accomplice.
TDP-43 turns up in the brains of 97 percent of ALS patients. It’s also found in other neurodegenerative diseases, including frontotemporal dementia, Alzheimer’s, and Huntington’s. In diseased cells, the protein shows up where it shouldn’t be found, outside the nucleus. And not only mislocalized, but truncated and clumped with other proteins in the surrounding cytoplasm of the cell. But the protein’s actual role in neurodegeneration has remained a mystery.
“The aggregates themselves are insoluble, so it’s hard to identify the component proteins,” he explains. Their plan was to use a method that identifies target proteins by examining the other proteins they associate with. While previously used with healthy cells, this method had not been tried on diseased cells, says Dr. Rossoll. Using this method, the authors determined that the aggregates interact with proteins that help transport substances between the cell’s nucleus and cytoplasm.Mayo Clinic neuroscientist Wilfried Rossoll, Ph.D., and his team set out to identify the proteins that exist within clumps, or aggregates, of TDP-43, a process he knew would be a challenge. Read the rest of the article on Discovery's Edge.
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