Multifunctional Zinc-Tannic Acid Nanoparticles Target α-Synuclein Aggregation and Oxidative Stress in Parkinson's Disease.

Abstract

In Parkinson's disease (PD), the abnormal aggregation of α-synuclein (α-Syn) and oxidative stress form a self-reinforcing vicious cycle that is a key driver of disease progression. To disrupt this pathogenic loop, this study designed and synthesized zinc-tannic acid coordination nanoparticles (Zn-TA NPs). Zn-TA NPs exhibit potent reactive oxygen species (ROS) scavenging capability and can concurrently inhibit α-Syn fibril formation and disaggregate α-Syn fibrils. In cellular models, Zn-TA NPs scavenged ROS, preserved mitochondrial function, and demonstrated neuroprotective effects. In a PD mouse model, treatment with Zn-TA NPs significantly improved motor and cognitive deficits, attenuated dopaminergic neuron loss, and reduced cerebral levels of α-Syn pathological deposition, oxidative stress, and neuroinflammation, without inducing significant systemic toxicity. These findings indicate that Zn-TA NPs exert multitarget neuroprotective effects by synergistically modulating α-Syn aggregation and oxidative stress, offering a novel strategy based on natural polyphenol-metal coordination for the treatment of neurodegenerative diseases.