Anionic nanoplastic contaminants promote Parkinson's disease-associated -synuclein aggregation

Recent studies have identified increasing levels of nanoplastic pollution in the environment. Here, we find that anionic nanoplastic contaminants potently precipitate the formation and propagation of alpha-synuclein protein fibrils through a high-affinity interaction with the amphipathic and non-amyloid component (NAC) domains in alpha-synuclein. Nanoplastics can internalize in neurons through clathrin-dependent endocytosis, causing a mild lysosomal impairment that slows the degradation of aggregated alpha-synuclein. In mice, nanoplastics combine with alpha-synuclein fibrils to exacerbate the spread of alpha-synuclein pathology across interconnected vulnerable brain regions, including the strong induction of alpha-synuclein inclusions in dopaminergic neurons in the substantia nigra. These results highlight a potential link for further exploration between nanoplastic pollution and alpha-synuclein aggregation associated with Parkinson's disease and related dementias.