Micro- and nanoplastics as neurotoxicants: Mechanistic insights from particle morphology, circadian disruption, and potential neurodegeneration - A state-of-the-art narrative review

초록

Micro- and nanoplastics (MNPs) are becoming increasingly ubiquitous in the environment, with emerging reports of their accumulation in animal and human tissues. Particle size, morphology, concentration, and surface functionalization modulate MNP cellular internalization, yet the roles of size and shape in toxicity remain underexplored. To address these gaps, we applied an AI-assisted search across fifty studies to uncover the most common outcomes of MNP exposure: inflammation and oxidative stress. A PRISMA-guided search was performed to investigate how these cascades influence microtubule disruption and revealed that neonatal tissues and tauopathy models in older populations (characterized by dynamic changes in the cytoskeleton) are more vulnerable to this disruption. A branch objective involved transcriptomic analyses of human major depressive disorder and murine circadian datasets to explore common inflammatory and clock gene networks that possibly amplify MNP toxicity. Finally, we reviewed the current state of research on how particle size and morphology influence toxicity, noting a paucity of mechanistic studies that used various particle sizes and shapes. This multifaceted framework underscores the need for additional studies on size-, shape-dependent toxicity mechanisms, and their association with cytoskeletal destabilization and neurodegenerative risk.

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