They figured out why we sometimes lose memory due to cancer

Until now, it was largely unknown what causes this “biological warfare,” in which the immune system itself can attack the brain, causing memory loss and rapid-onset cognitive deficits that can develop before a person even knows they have it. cancer.

Now a team of researchers from the University of Utah Health has discovered that some tumors can secrete a virus-like protein, triggering an out-of-control immune response that can damage brain cells.

Their findings were published in the journal Cell. In their study, the researchers focus on this rapid immunological attack because, as Jason Shepherd, an assistant professor of neurobiology at the University of Utah Health and the study’s final author, explains, “a rapid worsening of symptoms that can include changes in memory and behavior, loss of coordination, and even seizures.” are characteristic of a disease called anti-Ma2 (antibody-associated) paraneoplastic neurological syndrome.

The disease is part of a group of neurological syndromes associated with cancer. They occur in fewer than one in 10,000 people with the tumor.

The exact symptoms of these diseases vary, but they all involve rapid immune reactions directed against the nervous system.

“The symptoms come on quickly and can be quite debilitating,” Shepherd says.

“This exciting study shows how tumor cells can manipulate their environment,” said Neli Ullrich, executive director of the Comprehensive Cancer Center at the University of Utah Huntsman Cancer Institute.

Stacy L. Clardy, a neurologist at the University of Utah Health and co-author of the study, adds: “Most patients start experiencing these symptoms unusual neurological even before they know they have cancer.”.

These rapidly developing symptoms are the result of the immune system beginning to weaken. suddenlyattack certain proteins found in the brain.

Scientists knew that this germ often targets a protein called PNMA2. But no one knew why PNMA2 caused such a strong immune response, and researchers didn’t know how to prevent it.

“We don’t understand what’s happening at the cellular or molecular level that actually causes the syndrome,” Clardy says. “Understanding the disease mechanism is critical to developing more effective treatments,” he adds.

To figure out how PNMA2 initiates an immune response, Junjie Xu, a researcher at the university and lead author of the study, examined the protein’s structure using advanced microscopy.

When he saw the first clear image of the squirrel, he was “very, very excited,” Xu says.

The reason is that he observed several PNMA2 proteins spontaneously self-assembling into 12-sided complexes that had striking resemblance to the geometric protein layers of some viruses.

One of the functions of the immune system is to fight viruses. a structure similar to that of the PNMA2 virus makes it particularly vulnerable to attack.researchers found.

In fact, in experiments on mice, the immune system only attacked the PNMA2 protein when it was assembled into virus-like complexes.

Scientists have discovered that PNMA2 location in the body it is also a piece key puzzles.

“This protein is usually expressed only in the brain. in neurons, says Xu,but some cancer cells can express itwhat can trigger an immune response.

As long as PNMA2 remains in the brain, the immune system will not respond to it. But in rare cases, a tumor elsewhere in the body begins to produce the PNMA2 protein.

And when the immune system detects the PNMA2 protein outside the brain, it reacts in the same way as it would to any foreign invader. The immune system produces antibodies that bind to the unknown substance, and these antibodies direct the immune cells to attack.

But once activated, the immune system not only attacks the PNMA2 produced by cancer, but also targets parts of the brain that normally produce PNMA2, including areas involved in memory, learning and movement.

The brain usually has some degree of protection from the immune system, but cancer weakens this barrier

, leaving the brain especially vulnerable this immunological attack.

In future work, the researchers aim to figure out which aspect of the immune response is leading to rapid cognitive decline in patients: the antibodies themselves, immune cells making their way into the brain, or some combination of both.

Understanding how the immune system causes neurological symptoms could help scientists develop targeted treatments, as Shepard says: “If we show that PNMA2 antibodies are the culprits that actually cause neurological symptoms, we may be able to develop a way to block these antibodies.” not reaching the brain and not eliminating them with any treatment… If some of these neurological symptoms can be alleviated, that would truly be a huge achievement.”