ALS -- amyotrophic lateral sclerosis -- is a neurodegenerative disease that attacks motor neurons in the brain and spinal cord, slowly robbing its victims of their ability to walk, talk, breathe and swallow. In a cruel twist, some ALS patients also develop frontotemporal dementia, a disease that destroys an entirely different set of brain cells -- cortical neurons -- leading to personality changes, among other effects, according to a release posted to Eureka Alert.
Inherited forms of both diseases have been traced to gene mutations associated with an abnormal buildup of the RNA-binding protein, TDP-43, in the brain. Now, in a study in the journal eLife, Columbia University and New York Genome Center researchers show that TDP-43 and at least three other RNA-binding proteins appear to run similarly amok in ALS and dementia patients without the mutation. Their finding suggests that the dominant form of hereditary ALS and frontotemporal dementia may share molecular underpinnings with far more common versions of ALS and dementia that have no known genetic basis.
"It turns out that if you analyze the biochemical properties of RNA-binding proteins you see it's not just TDP-43 but several others that are also perturbed," says Aaron Gitler, a genetics professor at Stanford University who discusses the study in the same issue of eLife. "This is a new concept in how we think about these diseases - not just as TDP-43 diseases, but as RNA-binding protein diseases."
Normally, the TDP-43 protein helps control the expression of messenger RNA, and thus, gene behavior, from inside the cell nucleus. But in the brain cells of nearly all ALS and half of frontotemporal dementia patients, the protein accumulates outside the nucleus, eventually forming clumps big enough to see under a microscope. What causes the buildup, however, remains unclear.
You can see the full release at Eureka Alert.