Selenium nanoparticles functionalized by mushroom polysaccharides potentiated neuroprotection of selenium against Parkinson’s disease with lower toxicity

There is an urgent need to develop novel, oral agents that can prevent the occurrence of Parkinson’s disease (PD). Selenium (Se) plays a preventative role against PD, but there is great concern about its toxicity in clinical practice. We developed a novel extraction technology specifically tailored for the Cordyceps mycelium Cs4 polysaccharides-protein complex (PSP) and prepared the Se nanoparticles (Cs4-SeNPs) by using Cs4 PSP as capping agent, which has a well-characterized structure and high stability. The acute and sub-chronic toxicity of Cs4-SeNPs was demonstrated to be much lower than inorganic and organic Se. The preventative oral administration of Cs4-SeNPs could significantly improve motor functions and prevent dopaminergic neuronal loss in two PD animal models, but organic Se could not. Mechanism studies revealed that Cs4-SeNPs showed much higher antioxidant properties compared to inorganic or organic Se in PD animal and cell models. Cs4-SeNPs could protect against ROS-induced dopaminergic neuron apoptosis due to their strong antioxidant activities and by way of inhibition on the activation of ERs (endoplasmic reticulum stress) and PI3K/Akt/mTOR signaling pathway mediated autophagy in PD cell model. Our findings showed SeNPs functionalized by tailor-made Cs4 PSP enhanced the preventative neuroprotection of Se against PD with higher antioxidant activities and lower toxicity. This study provides solid scientific evidence for the development of an economical and safe oral agent in the prevention of PD.