Nanotechnology and nanomedicine hold potential to advance medical treatment through construction of materials with enhanced biological effects, at the atomic scale. By constructing nanopharmaceuticals, we may be able to design drugs with enhanced, focused effects, providing superior treatment for disease. In this study will examine the effects of cerium oxide nanoparticles, a potent nanoparticle antioxidant, in preservation of neuronal function in a preclinial model of Parkinson’s disease.
Our work in tissue culture and fruit fly models has shown that cerium oxide nanoparticles are potent free radical scavengers that provide enhanced and regenerative antioxidant activity that exceeds our traditional antioxidants. Our studies have shown that cerium oxide nanoparticles are neuroprotective in tissue culture models of Parkinson’s disease, and in the fruit fly. In this project, we will advance the investigation of cerium oxide nanoparticles to determine its utility in treatment of Parkinson’s disease, using a chemically-induced preclinical model of the disease. Models will be treated with cerium oxide nanoparticles, followed by induction of Parkinson’s disease with the chemical MPTP. We will examine neuronal degeneration and alterations in signaling molecules, and ascertain whether protection from neurodegeneration is afforded by cerium oxide nanoparticle treatment.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
If successful, this research will open up a new avenue for potential treatment for Parkinson’s disease using nanopharmaceuticals, which may preserve quality of life and prevent further neurodengeration is those afflicted with this disease.
Based on our preliminary work, we expect that cerium oxide nanoparticle treatment will protect dopaminergic neurons from degeneration and death associated with chemical induction of Parkinson’s-like disease. We expect to find enhanced survival of dopaminergic neurons, and preserved brain function. These studies will set the stage to bring this nanopharmaceutical into further study for potential human treatment.
In this project, we tested the hypothesis that pretreatment with cerium oxide nanoparticles prevented neurodegeneration in a pre-clinical model of Parkinson’s disease. We found that cerium oxide nanoparticles preserved striatal dopamine and protected neurons in the substantia nigra of a model challenged with the toxin MPTP, which induces Parkinson’s disease symptoms. Additionally, we determined the dose range for neuroprotective benefits, and examined the biodistribution of nanoparticles in the model – necessary prerequisites to further development of these nanoparticles as drug treatment. Our results identify cerium oxide nanoparticles as a novel, new nanopharmaceutical which may delay or halt the progression of PD.