Study identifies P2X7 receptor as drug target for brain inflammation

Researchers at the University of Birmingham identified the P2X7 receptor as an important driver of neuroinflammation, the inflammation of brain tissue, according to a study published in the journal Brain. The study was led by Professor Nicholas Barnes of the university's College of Medicine and Health, ScienceDaily reported on 7 October.

The team used live cultures of human brain cells and slices of brain tissue collected during neurosurgery. According to the report, P2X7 receptors promote the release of cytokines, proteins that help regulate inflammatory responses. When the researchers blocked the receptor with a specific antagonist, a drug that blocks a receptor, the inflammatory response in human brain tissue dropped significantly, the report said.

A major part of the work involved microglia, immune cells that help coordinate the brain's response to injury and inflammation. The researchers developed a method for converting human peripheral monocytes, a type of white blood cell collected from blood samples, into microglia-like cells. According to the report, this process mirrors a cellular transformation that has been identified as occurring naturally in the brain during human aging. When the researchers applied the antagonist, they interfered with signals released by the microglia-like cells as the cells became damaged and died, the report said.

Barnes said studying human microglia has long been a major challenge because the cells rapidly lose their defining characteristics once removed from their native brain environment. He described the monocyte-derived microglia as a scalable platform for studying human microglial biology. Barnes said the identification of the receptor marks a major step toward repurposing existing therapeutics to combat neuroinflammation at its source.

After the lab results, the researchers tested whether the findings could be reproduced in human brain tissue obtained through neurosurgical procedures, and the report said the successful results strengthen the case for further investigation. According to ScienceDaily, the work could eventually lead to clinical trials in people with neurodegenerative diseases or traumatic brain injury. The report said the findings could eventually have implications for traumatic brain injury, Alzheimer's disease, Parkinson's disease, depression and psychosis.