A study led by the University of Eastern Finland is the first to construct an integrated network combining RNA sequencing, microRNA sequencing, and DNA methylation analysis to investigate how ultrafine particles (UFPs) influence gene regulation in human cells. The findings were published in Environment International.

UFPs, primarily emitted from traffic, are the smallest yet highly concerning contributors to air pollution. They pose significant health risks to the brain and have been implicated in the development of neurodegenerative diseases such as Alzheimer’s disease (AD). Although air pollution is known to modulate gene transcription through epigenetic mechanisms like DNA methylation and microRNAs, UFP-specific effects remain underexplored.

The olfactory mucosa—located at the rooftop of the nasal cavity and directly exposed to the environment—serves as a critical entry point for airborne pollutants. Worryingly, UFPs deposit efficiently in this area. Environmental pollutants have been linked to olfactory dysfunction, an early clinical sign of AD. Professor Katja Kanninen’s research group at the University of Eastern Finland used a physiologically relevant human-based in vitro model of the olfactory mucosa, developed from cells donated in collaboration with Kuopio University Hospital.

The link between air pollution and Alzheimer’s disease is well established, but the molecular mechanisms remain poorly understood. Our study focuses on one key signaling pathway implicated in AD, helping to unravel how environmental stressors shape cellular responses, explains Laura Mussalo, Doctoral Researcher and first author of the study.

The researchers specifically examined changes in the PI3K/AKT signaling pathway, a critical regulator of cell growth and survival, which is known to be disrupted both in AD and by air pollution. Until now, the connection between UFP exposure, AD, and PI3K/AKT signaling had not been studied.

Their findings reveal that UFP exposure impairs PI3K/AKT signaling via a complex regulatory network involving epigenetic changes such as DNA methylation and microRNA activity. Many genes associated with the cell cycle and apoptosis were affected. Interestingly, despite these molecular alterations, significant cell death was not observed, suggesting that olfactory cells may possess adaptive mechanisms against environmental insults.

Additionally, the responses of cells derived from individuals with AD differed from those of healthy controls, indicating that AD cells may be more vulnerable to the harmful effects of UFPs.

This study offers important molecular evidence linking traffic-derived air pollution to gene regulation disruptions in the olfactory system and reinforces the role of environmental exposures in the pathogenesis of Alzheimer’s disease.

Source: https://www.uef.fi/en/article/traffic-related-ultrafine-particles-influence-gene-regulation-in-olfactory-cells