Mechanisms by Which Air Pollution Contributes to Parkinson's Disease
Most forms of air pollution (with a particular focus on fine particles) are now well established to contribute to age-related conditions at the level of exposure that is experienced in much of the industrialized world. Typically matters are worse in less wealthy regions, particularly those using solid fuel for domestic cooking and heating. Nonetheless, there is enough of a contribution even in wealthier regions for studies to show meaningful differences to health depending on varying levels of exposure. A study in the Puget Sound region, for example, found that greater exposure increased dementia risk.
The specific mechanisms by which air pollution accelerates the onset and progression of common age-related conditions are largely linked to chronic inflammation. Unresolved inflammatory signaling is disruptive to tissue structure and function, and the interaction of pollutants with cells in the lungs and airways promotes inflammatory signaling that affects the whole body.
Today's open access paper reviews what is known of these mechanisms in the context of a specific condition, Parkinson's disease. This neurodegenerative condition has a strong connection to the aging of the gut microbiome and intestines, as that is where the misfolded α-synuclein that drives the condition can originate. It then spreads through the nervous system to the brain, where it produces the first evident symptoms of Parkinson's disease, and eventually dementia and death. The greater the burden of inflammation placed upon body and brain, the faster this will happen.
Studies have reported positive correlations between exposure to particulate matter (PM), nitrogen oxide (NOx), ozone (O3), and an increased risk of Parkinson's disease (PD). Beyond the incidence of PD, studies have examined the linkage between long-term air pollution contact and the risk of hospitalization, mortality, and disease progression among PD patients, suggesting that air pollution may not only lead to the development of PD but also aggravate the clinical course and outcomes of the disorder.
Several pathways have been proposed to involve the biological processes underpinning the connection between air pollution and PD. Extensive research in animal models and human studies has reported that PD is interrelated with significant modifications in gut microbial structure, including the reduction of anti-inflammatory short-chain fatty acid (SCFA)-producing bacteria and the enrichment of opportunistic pathogens. Exposure to air pollution has been shown to disrupt the gut microbiome, potentially resulting in increased gut permeability, the propagation of pathogenic processes, and inflammation that may contribute to the development and progression of PD.
It has been demonstrated that interaction with air pollutants can also motivate α-synuclein to misfold and accumulate, as well as the impairment of other key proteins involved in neuronal function and homeostasis. Air pollution has been linked to oxidative stress and neuroinflammation, which can lead to the induction of multiple transcription factors, NRF2, NF-κB, and MAPK, forcing dopaminergic neurons to malfunction and degenerate. Furthermore, the incorporation of ultrafine PM in the brain, particularly in the olfactory bulb and other vulnerable zones, has been associated with excitotoxicity, mitochondrial dysfunction, and the propagation of neuroinflammatory processes that may be responsible for the pathophysiology of PD.
Despite progress in investigating the association between air pollution and PD, findings remain inconsistent. Some studies have recognized positive links between exposure to pollutants such as PM, NOx, and O3 and an increased risk of PD, whereas other studies have not found statistically important associations. These discrepancies underscore the complexity of the interactions between environmental exposures, genetic predisposition, and any other modifiable risk factors in the pathogenesis of PD. Mechanistic studies have offered useful insights into the biological pathways linking air pollution to PD. However, the precise mediators and dose-response relationships remain unclear. Furthermore, regional differences in pollution levels, exposure assessment methods, and population characteristics may contribute to the variability in findings across epidemiological studies. There is a growing need for well-designed, large-scale longitudinal studies with standardized exposure assessment methods to more accurately quantify the long-term effects of specific air pollutants on PD risk and progression.