Very tiny particles of cerium oxide — a compound with antioxidant effects — can prevent the toxic effects of alpha-synuclein in the brain, which may represent a new therapeutic option for Parkinson’s disease, a study suggests.
The study, “Nano-particle mediated inhibition of Parkinson’s disease using computational biology approach,” was published in Scientific Reports.
Several factors contribute to Parkinson’s disease progression, including the accumulation of alpha-synuclein proteins inside nerve cells and the formation of toxic protein aggregates called Lewy bodies.
Efforts have been made to develop pharmacological approaches to fight Parkinson’s, but no completely effective solution has been found yet.
Most pharmacological compounds are not specific and may result in severe side effects. Additionally, most available compounds are unable to cross the blood-brain barrier — a semipermeable membrane that protects the brain — and are not able to reach the nerve cells affected by Parkinson’s.
The use of nanoparticles loaded with an active agent have shown some promise in overcoming these limitations. The surface of these particles can contain small markers that allow them to pass through the blood-brain barrier and gain access to the central nervous system, specifically anchoring to the intended target cells and releasing their active pharmacological agent.
Now researchers are proposing the use of nanoparticles to target abnormal alpha-synuclein proteins.
The team designed a complete computer-based analysis of all known mechanisms concerning alpha-synuclein involvement in Parkinson’s to find the most suitable nanoparticle.
They compared three different nanoparticles: gold nanoparticles which have been shown to prevent alpha-synuclein aggregation; graphene and superparamagnetic iron-oxide nanoparticles that have also been reported to prevent fibrils formation; and cerium oxide nanoparticles that have been shown to have neuroprotective activity due to their antioxidant and anti-apoptotic effects.
Their analysis was based on compiled information about drug design and effects, disease diagnosis and features, as well as molecular target interactions and systems biology data.
Using computer simulation methods and protein modeling analysis, the team found that cerium oxide nanoparticles had a greater affinity toward alpha-synuclein, while sustaining good stability and overall response.
The analysis also revealed that cerium oxide could prevent the aggregation of alpha-synuclein, and promote the activation of dopamine receptors and the regulation of signaling pathways and genes important in Parkinson’s disease.
Based on these preclinical results, the researchers proposed cerium oxide nanoparticles “as [a] potential inhibitor of alpha-synuclein” that can “be employed as [a] nano-drug against Parkinson’s disease.”