Atmospheric Aerosol Neurotoxicity and Parkinson's Disease: Mechanisms and Perspectives

Parkinson's disease (PD) is a common neurodegenerative disease threatening the health of the middle-aged and elderly population, triggered by the combined effects of genetic susceptibility, environmental exposure and nervous system aging, among which atmospheric aerosol exposure is a key risk factor for sporadic PD. As a complex heterogeneous mixture, atmospheric aerosols contain neurotoxic components such as metal particles, persistent organic pollutants (POPs), and nano/ultrafine particles, which appear to target midbrain substantia nigra dopaminergic neurons through pathways including direct entry into the brain via the olfactory pathway, penetration across the lung-blood-brain barrier, and inflammation-mediated alterations in barrier permeability. The core molecular mechanisms that have been proposed to link aerosol exposure to sporadic PD include oxidative stress and mitochondrial dysfunction, neuroinflammation and aberrant microglial activation, disrupted protein homeostasis and abnormal aggregation of α-synuclein (α-syn), as well as altered epigenetic regulation. Moreover, neurotoxic effects may be amplified via the positive feedback loop of oxidative stress-neuroinflammation, the vicious cycle of mitophagy defects and protein aggregation, and the "multiple-hit hypothesis". This review summarizes the toxic components of aerosols, their brain-entry routes and pathogenic mechanisms, outlines the application status of emerging technologies such as in vitro cell models and in vivo animal models, and sorts out intervention strategies including pharmacological therapy and epigenetic regulation. It also analyzes the current challenges in research on mechanisms, models, population studies and intervention strategies, and points out that future research should focus on dissecting the synergistic mechanisms of multiple components and optimizing research models, so as to provide theoretical support for exploring potential strategies for precise prevention, control and treatment of PD.