Nanoplastic stimulates the amyloidogenesis of Parkinson's alpha-synuclein NACore

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 remains unknown. Here we employed electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS) to reveal the polymorphic oligomerization of NACore, a surrogate of alpha synuclein that is associated with the pathogenesis of Parkinson's disease. Our data indicated that the production rate and population of the NACore oligomers were modulated by their exposure to a polystyrene nanoplastic, and our cellular assays further revealed an elevated NACore toxicity in microglial cells elicited by the nanoplastic. Our simulations confirmed that the nanoplastic-NACore association was promoted by their hydrophobic interactions. These findings were corroborated by an impairment to 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.