Particulate Matter Induced Neurotoxicity: Interplay of Neuroinflammation and Organelle Dysfunction

Air pollution, composed of several complex particles, is regarded as one of the major causes of adverse health outcomes, and particulate matter (PM), which occurs primarily as PM10, PM2.5, and PM0.1 according to its aerodynamic diameter, is considered to be the most dangerous fraction. It is known to impair the healthy functioning of organ systems, including the cardiovascular system, respiratory system, gastrointestinal system, and reproductive system. Upon inhalation, the respirable fraction of PM can travel through the olfactory bulb and reach the brain, disrupting the blood-brain barrier (BBB), or act through peripheral responses, thereby causing neuroinflammation and oxidative stress in the brain. PM exposure activates unfolded protein response (UPR) and proapoptotic signals like CHOP and caspase-12, which drive brain cell death. It also impairs oxidative phosphorylation, increases ROS, and initiates mitochondrial permeability transition, which results in neuronal energy failure. Upon entering the system, it compromises the autophagic flux and lysosomal integrity, leading to its accumulation. Although the systemic effects of PM are widely recognized, its capacity to penetrate the central nervous system (CNS) poses a significant biological concern. This review maps how PM alters CNS components, leading to neuroinflammation and ultimately neurotoxicity, and examines the upstream and downstream mechanisms underlying these actions.