Nanoplastic Stimulates the Amyloidogenesis of Parkinson's Alpha‐Synuclein NACore

Abstract Environmental plastic wastes are potential health hazards due to their prevalence as well as their versatility in initiating physical, chemical, and biological interactions and transformations. Indeed, recent research has implicated the adverse effects of micro‐ and nano‐plastics, including their neurotoxicity, yet how plastic particulates may impact the aggregation pathway and toxicity of amyloid proteins pertinent to the pathologies of neurological diseases remains unknown. Here, electrospray ionization time‐of‐flight mass spectrometry (ESI‐TOF‐MS) is employed to reveal the polymorphic oligomerization of NACore, a surrogate of alpha‐synuclein that is associated with the pathogenesis of Parkinson's disease. These data indicate that the production rate and population of the NACore oligomers are modulated by their exposure to a polystyrene nanoplastic, and these cellular assays further reveal an elevated NACore toxicity in microglial cells elicited by the nanoplastic. These simulations confirm that the nanoplastic‐NACore association is promoted by their hydrophobic interactions. These findings are corroborated by an impairment in zebrafish hatching, survival, and development in vivo upon their embryonic exposure to the nanoplastic. Together, this study has uncovered the dynamics and mechanism of amyloidogenesis elevated by a nanoplastic trigger, shedding a new light on the neurological burden of plastic pollution.