Enzyme helps protect aging brains from memory loss and inflammation

An enzyme called PLA2G2F may help protect the aging brain from memory loss and inflammation, according to research reported by ERR. Experiments in mice found that the enzyme helped preserve memory and reduce inflammation, while analysis of human brain data suggested a possible natural defence against Alzheimer’s-related damage.

Researchers led by Cinzia Vicidomini and Amar Sahay searched the hippocampus, a brain region involved in forming memories, for genes that become active as the aging brain loses synapses, or connections between cells. They combined experiments on genetically modified mice with data on gene activity in individual human brain cells, comparing samples from healthy people, people with Alzheimer’s disease and people who retained sharp memories despite signs of the disease.

The gene responsible for producing PLA2G2F becomes more active with age, although young brains produce little of the enzyme. In the human data, it was especially active in older people who had Alzheimer’s-related damage but retained clear memories.

PLA2G2F breaks down fat molecules in cell membranes. The resulting substances act as signals that support communication between nerve cells and help maintain metabolic balance. In mice, the researchers found that this signalling helped prevent harmful fat droplets from building up inside brain cells.

When the researchers switched off the Pla2g2f gene in mice, the animals’ health deteriorated sharply. They lost nerve-cell connections, large fat droplets accumulated in their brain tissue, and severe inflammation developed. Older mice also struggled to remember new places and performed poorly in memory tests.

By contrast, older mice in which the researchers artificially increased Pla2g2f activity retained more nerve-cell connections and had memory as sharp as that of young mice. The intervention prevented memory loss in the animals.

Nerve cells produce PLA2G2F, but the enzyme also affects other brain cells, particularly microglia, which form part of the brain’s immune system and clear debris from tissue. Their function can falter with age.

The researchers also grew miniature brain models, known as organoids, from human stem cells to study interactions between nerve cells and microglia. When exposed to the enzyme produced by nerve cells, the microglia began releasing excess fat.