Unravelling the signaling power of pollutants

Exposure to environmental pollutants contributes to diverse pathologies, including pulmonary disease, lower respiratory infections, cancer, and stroke. Pollutants' entry can occur through inhalation, traversing endothelial and epithelial barriers, and crossing the blood–brain barrier, leading to a wide distribution throughout the human body via systemic circulation. Pollutants cause cellular damage by multiple mechanisms encompassing oxidative stress, mitochondrial dysfunction, (neuro)inflammation, and protein instability/proteotoxicity. Sensing pollutants has added a new dimension to disease progression and drug failure. Understanding the molecular pathways and potential receptor binding/signaling that underpin 'sensing' could contribute to ways to combat the detrimental effects of pollutants. We highlight key points of pollutant signaling, crosstalk with receptors acting as drug targets for chronic diseases, and discuss the potential for future therapeutics.