​Plastics, in particular microplastics (MP) and nanoplastics (NP), are a major environmental and health concern today because of their presence in all ecosystems and their high chemical stability. Highly hydrophobic, they penetrate living organisms through ingestion or inhalation and interact with biomolecules to form structures called biocoronas, consisting of a layer of biomolecules adsorbed on the surface of the particle. Following recent reports on the ability of MP and NP to cross the blood-brain barrier, the question of their interactions with brain proteins and possible toxicity has arisen. Human α-synuclein (hαSn) is a small presynaptic protein, abundant in the brain, genetically and neuropathologically associated with Parkinson's disease and Lewy body dementia.

In this study, it was chosen as a model to investigate its ability to bind with polyethylene (PE)-based plastics using molecular dynamics simulations and experimental methods. The results led to three important conclusions : i) hαSn changes from an open helical conformation to a compact conformation, which strengthens intramolecular interactions, ii) non-oxidised PE NPs rapidly adsorb hαSn, as shown by experimental dynamic light scattering data and adsorption isotherms, which modifies its structure, iii) oxidised NPs fail to capture hαSn. Interactions are mainly at the N-terminal domain of hαSn, with major contributions from hydrophobic amino acids.

These results could provide insights into the pathological basis of plastic nanoparticle-induced neurodegeneration, with the observed formation of the nanoparticle complex with human αSn constituting a plausible pathogenic driving force behind neurological damage and neuronal dysfunction.

Contacts : yves.boulard@i2bc.paris-saclay.fr ou yves.boulard@cea.fr et  jean-philippe.renault@cea.fr