The enigma of mitochondrial epigenetic alterations in air pollution-induced neurodegenerative diseases

Abstract

The incidence of neurodegenerative diseases is a growing concern worldwide, affecting individuals from diverse backgrounds. Although these pathologies are primarily associated with aging and genetic susceptibility, their severity varies among the affected population. Numerous studies have indicated air pollution as a significant contributor to the increasing prevalence of neurodegeneration. Cohort studies have provided compelling evidence of the association between prolonged exposure to different air toxicants and cognitive decline, behavioural deficits, memory impairment, and overall neuronal health deterioration. Furthermore, molecular research has revealed that air pollutants can disrupt the body's protective mechanisms, participate in neuroinflammatory pathways, and cause neuronal epigenetic modifications. The mitochondrial epigenome is particularly interesting to the scientific community due to its potential to significantly impact our understanding of neurodegenerative diseases' pathogenesis and their release in the peripheral circulation. While protein hallmarks have been extensively studied, the possibility of using circulating epigenetic signatures, such as methylated DNA fragments, miRNAs, and genome-associated factors, as diagnostic tools and therapeutic targets requires further groundwork. The utilization of circulating epigenetic signatures holds promise for developing novel prognostic strategies, creating paramount point-of-care devices for disease diagnosis, identifying therapeutic targets, and developing clinical data-based disease models utilizing multi-omics technologies and artificial intelligence, ultimately mitigating the threat and prevalence of neurodegeneration.