New research reveals that toxic air can reshape gene activity in the brain, potentially setting the stage for Alzheimer’s and Parkinson’s, underscoring the need for early detection and stronger protections for at-risk workers.
Review: Impact of Air Pollution and Occupational Inhalation Exposures on Neurodegenerative Disorders: an Epigenetic Perspective. Image Credit: IngeBlessas / Shutterstock
In a recent review article published in the journal iScience, researchers in Italy explored how air pollution contributes to neurodegenerative disorders (NDs) through epigenetic modifications. They highlighted the potential of using epigenetic markers to detect early changes triggered by air pollution, especially in high-risk groups. They stressed the need for further research to guide occupational and preventive health strategies.
Background
NDs are long-term diseases that involve the loss of nerve cells in the brain or nervous system, resulting in significant issues with memory, thinking, mood, and physical function. Alzheimer’s disease and Parkinson’s disease are the most common, affecting millions of people globally. As populations age, the number of people with these conditions is rising. Many cases are linked to preventable risk factors, including poor lifestyle habits, low education or income, and exposure to environmental pollution.
Air pollution consists of harmful particles and gases from natural sources, such as wildfires, and human activities, including fuel burning, traffic, and factory emissions. Particulate matter can carry toxic substances, including heavy metals, bacteria, and volatile chemicals. Though primarily associated with heart and lung diseases, air pollution is now also linked to brain damage and increased risk of NDs. Certain workers, such as miners, factory workers, and drivers, may be especially at risk.
How air pollution affects the brain
Air pollution can impact brain health through two primary pathways: direct and indirect. The direct pathway involves ultrafine particles and certain gases that can enter the bloodstream or travel through the nose to the brain, potentially damaging the blood-brain barrier (BBB) and causing inflammation. Some pollutants, such as nitrogen dioxide (NO₂), convert into active compounds that affect brain function, while others, like volatile organic compounds (VOCs), can accumulate in brain tissue due to their fat-soluble nature. Though evidence of direct brain effects from these pollutants remains limited, studies have shown that substances like nanoplastics, lead, and manganese can cross the BBB and harm brain cells.
The indirect pathway involves pollutants triggering inflammation or chemical signals (like cytokines, extracellular vesicles, or lung/brain-derived exosomes) in organs like the lungs or gut. These molecules then travel through the bloodstream to the brain, disrupting its balance and possibly leading to cognitive and emotional problems. Air pollution may also disturb gut and nasal microbes, affecting brain health through the gut-brain or olfactory-brain axes. While experimental evidence is still emerging, understanding these mechanisms may help identify early biomarkers of pollution-related brain damage, especially in at-risk populations like workers in polluted environments.
Epigenetic pathways
Epigenetic changes regulate brain function without altering deoxyribonucleic acid (DNA) sequences. These changes are vital for brain development, synaptic plasticity, and memory, but are also sensitive to environmental exposures, such as air pollution. Chronic exposure to pollutants can disrupt these epigenetic processes, potentially leading to NDs. Evidence suggests that such exposure may increase the expression of harmful genes, reduce the activity of protective genes, and alter non-coding ribonucleic acids (RNAs). These changes can occur long before symptoms arise, highlighting epigenetics as both a risk factor and an early biomarker for NDs.
Airborne pollutants can disrupt brain function by altering non-coding RNAs and DNA methylation, both of which regulate gene expression. Animal and human studies show these changes are linked to memory loss, inflammation, and NDs. However, most human evidence comes from peripheral blood samples, not brain tissue, limiting clinical interpretation. Toxins such as toluene, manganese, and lead can reduce the activity of protective genes or increase the production of harmful proteins in the brain. Some effects may even be passed to offspring. Air pollution also alters DNA methylation in blood and brain tissue, potentially increasing disease risk across the lifespan, especially with early or long-term exposure.
Few studies have explored how air pollution affects histone modifications in neurodegenerative diseases (NDs), due to technical challenges. However, early findings show links between air pollution and altered histone markers, DNA damage, and Alzheimer’s disease pathology in both humans and mice. Prenatal exposure to particulate matter affects brain development, particularly in males, due to impaired histone demethylation, highlighting sex-specific vulnerabilities. Plastic particles and heavy metals also disrupt histone modifications, causing oxidative stress, memory loss, and neuroinflammation. Notably, some experimental evidence for histone modifications (e.g., manganese-induced changes) comes from injection-based studies rather than inhalation exposure, creating uncertainty about real-world inhalation risks. Histone deacetylase inhibitors and compounds like butyrate (studied in lead-exposed mice) show potential in reversing some of these effects, offering avenues for future ND treatments.
Conclusions
Recent research shows strong links between air pollution and NDs mainly through epigenetic changes. Pollutants can alter DNA methylation, non-coding RNA expression, and histone modifications, all of which contribute to brain inflammation and damage. New methods like analyzing extracellular vesicles in blood may help detect these changes without invasive procedures. However, studying histone modifications remains technically challenging. Major gaps remain. Real-world air pollution is complex, making it hard to study precise effects. Factors like particle size, individual health, and early-life exposure influence risk but are not fully understood. Anatomical differences between animal models and humans (e.g., nasal structure) further complicate translation of inhalation studies. Most research focuses on older adults, short-term exposure, and a limited number of pollutants, overlooking long-term and early-life effects. Diseases like multiple sclerosis, amyotrophic lateral sclerosis (ALS), and Huntington’s disease are also under-researched.
Future studies should be long-term, include younger populations, and consider less-studied pollutants and exposure routes, such as diet or gut-brain interactions. Combining omics technologies and artificial intelligence could help identify biomarkers and lead to the development of preventive therapies. Improved workplace and environmental protections, especially for high-risk groups, are also essential to reduce ND risk. Addressing regulatory implications requires validating epigenetic tools for clinical use.