A Three-Pronged Attack On Parkinson’s Disease

A research group in South Korea has developed a set of three nanoparticles with differing properties to remove reactive oxygen species in various cellular compartments.

AsianScientist (Aug. 10, 2018) – A team of researchers in South Korea has developed nanoparticles that could be used to treat Parkinson’s disease. Their findings are published in Angewandte Chemie.

Parkinson’s disease is characterized by the sudden degeneration and death of neurons that secrete dopamine in the brain. The accumulation of reactive oxygen species can contribute to the onset of mitochondrial dysfunction, neuroinflammation and neuronal death. The brain’s low antioxidant levels and abundance of lipids make it more vulnerable to the side effects of reactive oxygen species.

In the present study, researchers at the Institute of Basic Science (IBS) in South Korea developed three types of ceria nanoparticles with different sizes and surface properties to selectively remove reactive oxygen species from mitochondria and intra- and extracellular spaces.. Ceria nanoparticles are nanoparticles with cerium ions on their surfaces, which switch between Ce3+ and Ce4+ in the presence of reactive oxygen species. They mimic the activity of natural antioxidants, like catalase and superoxide dismutase.

The researchers demonstrated that ceria nanoparticles with a size of 11 nm and a negative surface charge of -23 mV were small enough to enter neurons but could not pass through the mitochondria membrane, thus allowing specific targeting of intracellular spaces.

To allow the ceria nanoparticles to enter the mitochondria, the researchers decorated the ceria nanoparticles with triphenylphosphonium (TPP), which confers the nanoparticles with a positive surface charge of +45 mV.

The researchers also developed a third version of the ceria nanoparticles which involved hundreds of thousands of 3 nm ceria nanoparticles aggregating to form a negatively charged cluster with a size of 400 nm. Being too large to enter cells, these clusters can remove reactive oxygen species outside of cells.

The researchers then treated mice with these three types of nanoparticles, delivering the nanoparticles to a part of the brain called the corpus striatum. Because Parkinson’s disease involves declining levels of the neurotransmitter dopamine in the brain, the researchers proceeded to assess the expression of tyrosine hydroxylase—an enzyme required to produce dopamine—in mice receiving the nanoparticle treatment.

When reactive oxygen species in the extracellular spaces were removed using clusters of ceria nanoparticles, neuroinflammation was reduced, but oxidative stress persisted and tyrosine hydroxylase expression continued to decrease. However, when the mice were treated with the negatively charged ceria nanoparticles and the TPP-ceria nanoparticles, tyrosine hydroxylase levels were higher than those in control mice. The results suggest that Parkinson’s disease can be treated by lowering oxidative stress in the intracellular and mitochondrial compartments of neurons.

“These experiments have identified the essential role of intracellular and mitochondrial reactive oxygen species in the progression and treatment of Parkinson’s disease. We hope that the ceria nanoparticle system will be useful tools for developing therapeutic agents in diseases that involve oxidative stress, as well as other degenerative diseases,” explained Dr. Kwon Hyek Jin of IBS, the first author of the study.



The article can be found at: Kwon et al. (2018) Ceria Nanoparticle Systems for Selective Scavenging of Mitochondrial, Intracellular, and Extracellular Reactive Oxygen Species in Parkinson’s Disease.

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Source: Institute for Basic Science; Photo: Shutterstock.
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