Several genes have been linked to ALS, with one of the most recent called FUS. Two new studies in PLoS Biology, one from the University of Pennsylvania School of Medicine, and the other from colleagues at Brandeis University, both examined FUS biology in yeast and found that defects in RNA biology may be central to how FUS contributes to ALS, or Lou Gehrigâs disease. These findings point to new targets for developing drugs.
Proteins aggregate to form insoluble clumps in the brain and spinal cord of ALS patients. In some instances of ALS, the clumping protein is FUS, while in other cases it is another protein called TDP-43. FUS and TDP-43 are both RNA-binding proteins with similar features. For example, both proteins contain a region that is remarkably similar to the type of section that enables some proteins to form prions in yeast. Prions are rogue infectious proteins that cause mad cow disease in cattle and CreutzfeldtâJakob disease in humans. Despite these similarities it was not clear if TDP-43 and FUS both contribute to ALS in similar or different ways.
In 2009, two groups found mutations in the FUS gene in some ALS patients. In the same year, co-senior author Aaron Gitler, PhD, assistant professor of Cell and Developmental Biology, used a yeast model to study FUS and to determine what effect those mutations were having on its function. Meanwhile, co-senior author James Shorter, PhD, assistant professor of Biochemistry and Biophysics, purified the FUS protein and studied the properties that made it readily form clumps. Gitler and Shorter had previously teamed up to study TDP-43 in yeast cells and pure protein assays. âThis is an exciting time. The picture is really coming together for the molecular players in ALSâ says Gitler.
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