ALS, identified a protein whose presence may contribute to the development of the disease

There amyotrophic lateral sclerosisalso known as Lou Gehrig’s disease from the name of the legendary American baseball player who (perhaps) died of it in 1941, is the most common form of motor neuron disease. This type of pathology, explains the Msd Manual, «are characterized by a progressive deterioration of the nerve cells involved in muscle movement. This in turn leads to a deterioration of the muscles stimulated by these nerves, which weaken and are no longer able to function normally. These diseases can involve the central nervous system (the brain and spinal cord) as well as the peripheral nervous system (nerves outside the brain and spinal cord). There are no curative cures but only therapies to contain the symptoms. One study of California University-Boulder now seems to allow us to hope for a step forward in understanding the disease. He did so by identifying a new element involved in the development: a ‘ancient viral protein known among other things, and paradoxically, for its essential role in the development of the placenta in pregnant people.

The global incidence of ALS is 1.7 cases per 100,000 people/year, with about a thousand new cases a year in Italy, even if some estimates raise the threshold to 2 thousand. Global prevalence is currently estimated to be around 200/300 thousand cases, about 5/6 thousand in Italy. ALS is the same disease that struck unforgettable sports champions such as Stefano Borgonovacenter forward of Baggio’s Fiorentina and Van Basten’s AC Milan, as well as the brilliant scientist Stephen Hawking who discovered in 1963, at the age of 21, that he was ill. And again, among others, the former footballers Gianluca Signorini, Armando Segato (the first case in Italy), Giorgio Rognoni, the radical exponent Luca Coscioni and jazz great Charles Mingus.

The survey, published in the specialized magazine eLifesuggests that “when this strange protein known as PEG10 is present at high levels in nervous tissue, changes cellular behavior in ways that contribute to ALS.” These are the words of the main author of the investigation Alexandra Whiteleyassistant professor of biochemistry at the University of California.

With funding from the Als Association, the National Institutes of Health and other funders, his lab is now working to understand the molecular pathways involved and obviously to find a way to inhibit the excessive proliferation of the protein. “It’s still early days but the hope is that these investigations could potentially lead to an entirely new class of potential therapies to get to the root cause of this disease.”

What exactly is PEG10

We need to frame the question in a broader key: more and more research suggests that more or less the half of the human genome it is made up of DNA fragments left behind by viruses, known as retroviruses, and by “mobile” DNA sequences, i.e. capable of moving from one gene location to another without respecting predetermined rules. In many cases they would be the result of agents that even infected our primate ancestors 30-50 million years ago.

PEG10, or Paternally Expressed Gene 10, is one of these «domesticated retrotransposons», precisely fragments of DNA capable of autonomously transcription in an intermediate to RNA, become DNA and then insert themselves in different positions within the genome. Studies show that it probably played a key role in the allow mammals to develop placenta, a fundamental step in human reproduction. However, when it’s overly plentiful it can also fuel disease, including some cancers and another rare neurological disorder called Angelman syndrome. We now know that it probably also plays a role in ALS.

Whiteley focuses his research on how cells get rid of the abundant proteins often implicated in other neurodegenerative diseases including Alzheimer’s and Parkinsons. In his laboratory we study, as in a handful of other places in the world, a class of genes called ubiquitous, which serve precisely to prevent the accumulation of problematic proteins in cells. In 2011, in particular, a study linked a mutation in the gene ofubiquilin-2 (UBQLN2) to some cases of familial ALS, which constitutes about 10% of cases of cases. The other 90% is in fact random. But it has not been clarified how the faulty gene could fuel the disease of this type.

Using laboratory techniques and animal models, Whiteley and colleagues at Harvard Medical School first set out to determine which proteins end up accumulating when UBQLN2 fails at its job and fails to curb its accumulation. Among thousands of possible proteins, PEG10 tops the list. Later the team collected the spinal tissue of deceased and ALS patients (provided by the Target Als medical research foundation) and used protein analysis, or proteomics, to check which ones were overexpressed. Again, among more than 7,000 possible proteins, PEG10 appeared in the top five both in cases of familial and sporadic ALS.

In a separate experiment, the team then found that if ubiquilin does not do its job effectively, the PEG10 protein accumulates and interrupts the development of axonsthe long, thin nerve fibers that carry electrical signals between each other and generally from the brain to the body.

“The fact that PEG10 is likely contributing to this disease means we may have a new target for treating ALS for a terrible disease in which there are no effective therapies that extend life any longer.” of a couple of months, it could be a huge step forward.’

Not only that: this line of research could also lead to one better understanding of other diseaseswhich replicate the same dynamics and derive from the accumulation of proteins, as well as a deeper insight into how ancient viruses affect health.

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