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ALS patients: ancient viral heritage sheds light on disease etiology

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ALS patients: ancient viral heritage sheds light on disease etiology

The genetic legacy of an ancient virus may help shed more light on the origin of amyotrophic lateral sclerosis (ALS). PEG10 is one of countless viral genes previously in the human genome that have taken on novel tasks in various tissues. The most important is to help form the placenta. But now researchers led by Alexandra Whiteley of the University of Colorado at Boulder (UC Boulder) Increased levels of PEG10 protein in neural tissues of ALS patients is found.

Normally, a gene called ubiquilin 2 provides the right amount of PEG10. However, in ALS patients, the regulating gene is often mutated and no longer slows down PEG10 production. The researchers wrote in the journal eLife that the ubiquitin-2 mutation was already known, but it was not clear how it leads to disease progression.

More from MIT Technology Review

More from MIT Technology Review

More from MIT Technology Review

More from MIT Technology Review

So they are looking in cell cultures and animal experiments for proteins that accumulate when this mutation is present. PEG10 ended up at the top of the list. When they then examined the spinal cord tissue of the deceased ALS patients, PEG10 was also one of the five most frequently reported proteins here.

As Whitley’s team discovered in other experiments, excess PEG10 interferes with the reading of various genes and, as a result, impedes the formation of the nerve cell’s long nerve process, called the axon. However, these usually transmit electrical control signals from the brain to the muscles.

ALS, also known as Lou Gehrig’s syndrome, is a fatal neurodegenerative disease. It gradually destroys the motor neurons in the brain and spinal cord so that they can no longer transmit brain control commands to the muscles. The result is muscle paralysis. Patients are deprived of their ability to move, swallow, speak and breathe.

ALS can also be associated with dementia that develops in the frontal and temporal lobes of the brain, resulting in personality and behavioral changes (frontotemporal dementia). The hereditary form of ALS accounts for about ten percent of all cases. However, in 90% of cases, the disease occurs “sporadically”, that is, suddenly. The PEG10 gene is transcribed very strongly in both groups.

According to the German Center for Neurodegenerative Diseases h. According to V. Up to 9,000 people have ALSAbout 2,500 new cases are added each year. Physicist and cosmologist Stephen Hawking was one of the most famous patients with ALS.

Some medications can slow the progression of the disease. However, there is no cure. Therefore, Whitley and colleagues hope that “a better understanding of the biology of PEG10 in the context of ALS and other diseases in which PEG10 is elevated may open new avenues for developing treatments,” they write in their publication.

“The fact that PEG10 is likely to contribute to this disease means that we may have a new target for treating ALS,” Whitley told the University of California, Boulder. “For a terrible disease that doesn’t have effective treatments that extend life expectancy by more than a few months, this could be very important.”

With financial support from the ALS Society, the US National Institutes of Health, and project partners, her group is now trying to elucidate the molecular pathways involved and find an approach to inhibit the recalcitrant protein. Whiteley has filed a patent for the use of PEG10 as a biomarker and diagnostic aid for ALS.

The PEG10 gene once encoded part of the virus envelope. It is estimated that such retroviral genes make up up to 50 percent of our DNA. Retroviruses contain RNA as their genetic material, and write it into their DNA after infecting cells so that the cell reads it and builds new virus particles. This is how the HI virus works, for example. But many earlier, often ancient, retroviruses lost their fangs, so to speak, when parts of their genome were incorporated into ours.

These pieces of DNA, called retrotransposons, that can migrate into the genome, are inherited, but no longer produce viral particles. They were, as biologists say, domesticated. Just as wild animals after domestication no longer bite but rather support their owners, so reverse transposons serve us in various functions. In some cases, such as PEG10 with its placenta-forming properties, it has even been able to achieve an evolutionary leap in evolution.

However, in the wrong tissues, excess can also lead to disease. This is no stranger to PEG10: Too much of it has also been linked to the neurological condition Angelman syndrome, in which it disrupts brain development at the embryonic stage. Excessive production can also lead to different types of cancer such as liver cancer and chronic lymphocytic leukemia.


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