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The extensive distribution of microplastics (MPs) in the environment and their food chain contamination urgently necessitates a deeper understanding of their molecular-level impact on physiological responses. This study employed a mass spectrometry-based proteomics approach to investigate the potential risks, mechanisms of associated cellular processes, and biological reactions to preformed protein-MPs coronation and intact MPs using brain-derived neuronal and glial cells. Our findings indicate that MPs can adsorb proteins and form a heterogeneous corona layer when interacting with biological fluids such as serum. Proteomics analysis revealed that protein-MP coronation notably alters protein expression levels compared to intact MPs, impacting core cellular biological processes, including protein synthesis machinery and RNA processing pathways, lipid metabolism, and nuclear-cytoplasmic compartmentalization and transport. Notably, the heterogeneous protein adsorption onto MP surfaces perturbs a wide range of cellular signaling pathways through cellular recognition mechanisms, potentially contributing to the challenge of MP accumulation in the brain.
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