Fundamental pathology behind amyotrophic lateral sclerosis
The researchers were led by J. Paul Taylor, M.D., Ph.D., chair of the St. Jude Cell and Molecular Biology Department and a Howard Hughes Medical Institute investigator; and Rosa Rademakers, Ph.D., of the Mayo Clinic in Jacksonville, Florida. The findings appear today in the journal Neuron . The disease-causing mutation identified is the first of its kind, Taylor said. Unlike in other genetic diseases, the mutation does not cripple an enzyme in a biological regulatory pathway. Rather, the mutation produces an abnormal version of a protein involved in a process called phase separation in cells. Phase separation is a mechanism by which proteins assemble into organized assemblies, called membrane-less organelles, necessary for orderly cell functions. The researchers found that the ALS/FTD mutation produces an abnormal version of a protein called TIA1 that is a building block of such organelles. As a result, in ALS, the proteins accumulate and kill neurons that control muscles....