Micro-/nano-plastics accentuate Parkinson's Disease-relevant phenotypes in a Drosophila model

Micro- and nano-plastic (MNP) particles are a ubiquitous environmental contaminant that are increasingly bioaccumulating in human tissues, particularly the brain. MNPs induce mitochondrial defects, oxidative stress, inflammatory responses and neurotoxicity in cellular and organismal models. This raises the possibility that MNP exposure could cause or exacerbate neurological conditions associated with these pathological phenomena. Parkinsons Disease (PD), a common movement disorder characterised by degeneration of striatal dopaminergic neurons, and associated with mitochondrial dysfunction, represents such a condition. We therefore hypothesised that MNP exposure might interact with PD risk mutations affecting mitochondrial fidelity. We used a fruit fly model of PRKN-dependent PD associated with defects in mitophagy, a mitochondrial quality control pathway, to test this hypothesis. We found that ingestion of MNPs at concentrations tolerated by wild-type controls selectively enhanced PD-relevant phenotypes - including progressive dopaminergic neurodegeneration, movement defects, and sleep disruption - in this model of PD. Our data suggest that defects in mitochondrial quality control can increase vulnerability to MNP exposure, and more broadly, that MNPs may synergistically interact with existing genetic risk factors to worsen neurological disease.