'Master genes' may explain why some NFL players develop brain diseases

brain
UCLA scientists have discovered a set of genes that may become damaged in brain-injury patients and put them at risk of future neurological diseases.

Reports of neurological disorders among retired National Football League players sparked a massive medical debate and an estimated $1 billion settlement paid by the NFL last year to settle lawsuits from former stars who sustained head injuries. Now, scientists at the University of California in Los Angeles say they have uncovered a set of “master genes” in the brain that can be damaged by traumatic brain injuries. The discovery might explain why people who suffer head injuries develop Alzheimer’s and other diseases many years later—and it could provide new targets for drugs to treat them.

The scientists, led by UCLA professors Xia Yang and Fernando Gomez-Pinilla, believe the master genes that they identified control hundreds of other genes that have been linked to Alzheimer’s, depression, Parkinson’s and many other brain disorders, according to a press release from UCLA. When the master genes become damaged by traumatic injury, a ripple effect can occur that causes other genes in the chain to produce irregular proteins.

To find the genetic culprits, the UCLA team trained 20 rats to escape from a maze, then used a fluid to simulate brain injury in half of them. After confirming that the injury impeded the rats’ ability to complete the maze, the scientists took samples of RNA from both their brains and their blood. They found 268 genes in the brain that had been altered in response to the simulated injury, and 1,215 changed genes in the white blood cells.

"A surprise was how many major changes occurred to genes in the blood cells," Yang said in the release. The finding was significant because white blood cells play a key role in the immune system. Yang believes the experiment showed that when the brain was damaged, it sent signals to the immune system that the body was under attack, which then caused the genetic changes. More than 100 of the changed genes are similar to those in people and have been linked to neurological diseases. The research was published in the journal EBioMedicine. 

Yang and her team see two potential uses for their catalog of genes that are altered by traumatic brain injury. They could give scientists ideas for new drugs to treat Alzheimer’s and other diseases, they say. And perhaps in the long term, they could lead to new ideas for repairing the master genes to reduce the future risk of brain disorders.

There are many efforts underway around the world to ward off deleterious effects of brain injuries. Researchers at the Hebrew University of Jerusalem, for example, are developing molecules called thioredoxin-mimetic peptides (TXM-peptides), which inhibit particular inflammation-causing enzymes and thereby seem to reverse the effects of mild traumatic brain injury. And the University of Miami is teaming up with Boston-based Tetra Discovery to test an inhibitor of PDE4B, which has been implicated in inflammation caused by traumatic brain injuries.

The UCLA team plans to study the master genes they identified to see if modifying them also changes the other genes they control. Then they hope to study the same genes in people who have suffered from traumatic brain injuries.