Biologically-synthesized zinc oxide nanoparticle-based α-synuclein nanoformulation mitigates Parkinson's disease progression in Drosophila melanogaster.

Parkinson's disease (PD) is a synucleinopathy characterized by the accumulation of alpha-synuclein (αS) amyloid aggregates and loss of dopaminergic neurons. Evidence suggests that PD originates in intestine and progresses to brain via the vagus nerve. Thus, initially, the potential of orally-fed αS pre-formed fibrils (PFF) to induce PD in the wild-type Drosophila melanogaster is explored, where the findings corroborate the hypothesis of retrograde transport of infection from gut-to-brain, and exhibit PD-like symptoms, including impaired motor and non-motor symptoms, and degeneration of dopaminergic neurons. However, the PD flies, when transferred to green-synthesized zinc oxide nanoparticle surface-adsorbed αS nanoformulation (NF)-supplemented feed, show respite from progressive PD by restoring the retromer complex expression that induces the autophagic clearance of accumulated pathological PFF and ameliorating the oxidative stress and inflammation. Overall, the findings demonstrate therapeutic potential of the NF against the progressive PD.