RARE Daily

Discovery Points Toward Approach to Treating Set of Rare Diseases

December 7, 2020

Rare Daily Staff

University of Minnesota researchers have discovered a potential target for the research and development of future therapies to mitigate the symptoms of a series of genetic disorders called laminopathies.

Laminopathies cause a wide range of conditions including skeletal muscular dystrophy, neuropathy, and premature aging.

In a study published in the Proceedings of the National Academy of Sciences, researchers sought to understand how mutations in proteins that associate with the nuclear envelope — which encases each cell’s nucleus—cause laminopathies.

Scientists examined the interactions between proteins within the nuclear envelope of Caenorhabditis elegans, a worm used for some types of medical research. They found that torsinA interacts with the lamin protein, which provides structure inside the nucleus, and with components of the LINC complex, which transmits mechanical signals and forces across the nuclear envelope. When the lamin protein is mutated in the worms, the life span, development of reproductive organs, and the viability of off-spring are negatively impacted.

“One of the proteins that we are interested in is torsinA. When this protein is not working properly in humans, it can cause a disease called early-onset dystonia, which has no cure and causes uncontrollable muscle contractions,” said study lead Gabriela Huelgas Morales, a postdoctoral associate in the College of Biological Sciences. “We wanted to find out how this protein works and what could be done to help cells maintain their normal functions.”

The researchers found that worms with the mutated lamin have frail nuclei that are prone to rapid collapse, a new phenomenon with relevance to laminopathies. They found that decreasing the function of torsinA in worms with mutated lamin proteins prevented nuclear collapse and extended the worms’ lifespan. And they found that torsinA promotes the function of the LINC complex.

“While there is much more research to be done, these findings point to possible future opportunities to create therapies to target the torsinA–LINC complex nexus,” said study co-author David Greenstein, a professor and the associate dean of research in the College of Biological Sciences. “In doing so, cells can maintain their structure and potentially alleviate symptoms caused by laminopathy diseases.”


Photo: David Greenstein, a professor and the associate dean of research in the College of Biological Sciences at the University of Minnesota

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