Scientists have delineated how an enzyme drives neuroinflammation in mice by triggering immune cells called microglia, according to work involving cultured cells and mice. In addition to identifying a new inflammatory mechanism in the brain, their work hints that the enzyme, named GCN5, could be a target in Alzheimer’s disease, multiple sclerosis, and other disorders that are intimately linked to neuroinflammation. This form of inflammation can occur in the aftermath of infections and brain injuries or with neurodegenerative disorders. Often, these insults trigger strong responses from microglia, large immune cells that normally monitor and protect the central nervous system. When activated, the microglia release inflammatory factors such as TNF-α, which over time can damage and kill the remaining healthy neurons. In this study, Duk-Yeon Cho and colleagues investigated the role of GCN5, an enzyme that has previously been linked to inflammation in other parts of the body. In a mouse model, the team found that inducing inflammation with a bacteria-derived molecule boosted amounts of GCN5 throughout the body, including in the brain. Inflammation also led to a spike in microglia, which then released pro-inflammatory molecules such as TNF-α, IL-6, and COX2. Studies of cultured microglia showed that GCN5 triggered neuroinflammation by modifying the transcription factor NF-κB, thus allowing the factor to migrate to the nucleus and support the transcription of inflammatory mediators. “Our findings suggest that neuroinflammation might be controlled by pharmacologically modulating GCN5 activity or expression levels, revealing a new avenue for drug development,” Cho et al. write.

A new study uncovers crucial insights into the gene interactions linked to Alzheimer's disease (AD), revealing how amyloid-beta accumulation affects gene dynamics across different brain regions and age groups.

Groundbreaking research shows human brains contain approximately a spoon's worth of microplastics, with dementia patients showing 3-5 times higher concentrations. The findings, highlighted in a new Brain Medicine Commentary, reveal concerning trends in brain tissue contamination and potential links to neurological disorders.