Mount Sinai Researchers Establish Link Between Amyotrophic Lateral Sclerosis and the Body’s Response to Viral Infection

Mount Sinai Researchers Establish Link Between Amyotrophic Lateral Sclerosis and the Body’s Response to Viral Infection

shutterstock_118491940In a recent study titled “Senataxin suppresses the antiviral transcriptional response and controls viral biogenesis,” published in the journal Nature Immunology, researchers at Mount Sinai Hospital/Mount Sinai School of Medicine found that a human protein called senataxin (SETX), which has been found to be associated with neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), plays an important role in the response to viral infection.

Neurological diseases are associated with inflammation as an innate immune response to infection representing the first line of cellular defense against invading pathogens. Findings from this new research study indicate that specific genetic alterations make senataxin less capable of moderating the inflammatory response to particular pathogens, which can lead to persistent inflammation and disease progression.

Through the use of genomics, the researchers were able to find that senataxin plays a role in controlling the body’s antiviral response, however without this capacity, an exposure to anti-viral response can lead to persistent inflammation. According to the researchers, patients with ALS and ataxia have mutations in SETX, and are less able to regulate the anti-viral response.

“We knew this protein was important, but its precise activity and role in the antiviral response had never been demonstrated before,” said Harm van Bakel, co-author of the paper and Assistant Professor in the Department of Genetics and Genomic Sciences and in the Icahn Institute of Genomics and Multiscale Biology at Mount Sinai in a recent news release. “Teasing out the function of senataxin required an interdisciplinary approach that would not have been possible without international and cross-department collaboration and the advanced technology resources available at Mount Sinai.”

Most of the genomic studies have been conducted in yeast cells, however, for this study, Mount Sinai researchers used human and animal models and found that senataxin has far more power to regulate gene activity than was previously thought.

“This is a protein implicated in neurodegenerative disease that has now been linked to our innate antiviral mechanism, and it offers an intriguing clue to a relation between the inflammatory response and these diseases,” said Ivan Marazzi, co-author of the paper and assistant professor of microbiology at Mount Sinai in the news release. “Whether viral infection plays a role in disease progression remains to be seen, but this discovery has broad implications for biomedical research and opens up new avenues that we look forward to pursuing.”

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