Citric Acid CQDs Shown to Protect Dopaminergic Neurons in Models

Parkinson's treatment may lie in carbon quantum dots derived from antioxidant

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by Steve Bryson, PhD |

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Nanomaterials with potent antioxidant properties called carbon quantum dots prevented Parkinson’s disease-related neurodegeneration in nerve cells and a worm model, a study reported.

These antioxidants, especially those derived from citric acid — a common and nontoxic biochemical — may represent a new treatment approach for Parkinson’s and other neurodegenerative diseases, its researchers noted.

The study, “Citric Acid-Derived Carbon Quantum Dots Attenuate Paraquat-Induced Neuronal Compromise In Vitro and In Vivo,” was published in the journal ACS Chemical Neuroscience.

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Oxidative stress, or the imbalance between the generation and clearance of tissue-damaging reactive oxygen species (ROS), is thought to play a role in neurodegenerative diseases.

In Parkinson’s, evidence suggests that ROS contributes to the loss of dopaminergic neurons, nerve cells that produce the signaling molecule dopamine. Their loss, and the resulting drop in dopamine levels, leads to Parkinson’s symptoms.

Citric acid CQDs aid nerve cell survival after toxin

Designing molecules with high antioxidant activity and good tolerability is a potential therapeutic approach in neurodegenerative disease management.

Carbon nanomaterials are a class of materials widely used to deliver therapeutics, and used in biomedical imaging, biosensors, tissue engineering, and cancer treatment.

Carbon quantum dots (CQDs) are a class of carbon nanomaterials — with ROS savaging properties — often created from biodegradable waste using environmentally friendly methods. Studies suggest that CQDs can protect cells exposed to the MPTP neurotoxin, which has been shown to cause Parkinson’s-like symptoms in rodents and humans.

Citric acid is a common precursor for the preparation of CQDs because of its low toxicity and high biocompatibility. However, whether CQDs derived from citric acid (Cit-CQDs) have antioxidant properties clinically relevant to Parkinson’s is unknown.

Researchers at the University of Texas at El Paso tested the protective properties of Cit-CQDs in human nerve cells and a roundworm (Caenorhabditis elegans) exposed to paraquat. Paraquat, a herbicide or weed-killer in worldwide use, has a similar structure to MPTP, and case-controlled studies have found an association between Parkinson’s and paraquat exposure.

C. elegans is a species of tiny transparent worms without a bloodstream or respiratory system but with dopaminergic neurons that can be monitored directly.

“We were interested in demonstrating the prophylactic effect of Cit-CQDs and their ability to prevent neuronal cell death by scavenging and inhibiting [Parkinson’s disease],” the researchers wrote.

The team first showed that Cit-CQDs savaged ROS in a dose-dependent manner in a solution, confirming their antioxidant potential.

Human nerve cells then exposed to paraquat demonstrated a dose-dependent rise in cell death. In comparison, except for the highest dose tested, increasing levels of Cit-CQDs did not affect cell survival. When combined, Cit-CQDs’ presence significantly protected the cells from death at all doses tested.

Paraquat exposure also triggered an increase in ROS within the nerve cells, whereas the addition of Cit-CQDs alone had no impact on ROS levels compared to untreated control cells. Nerve cells exposed to paraquat and treated with Cit-CQDs showed a significant reduction in intracellular ROS, suggesting that “Cit-CQDs mitigate [paraquat]-associated oxidative stress in cells,” the researchers wrote.

Similar to human cells, survival of roundworms exposed to paraquat declined in a dose-dependent manner, while the four doses of Cit-CQDs alone had no effect. The roundworms were then incubated with Cit-CQDs before exposure to paraquat at a dose known to elicit 50% mortality. Cit-CQDs significantly improved roundworm survival.

In a final experiment, researchers tested the impact of paraquat and Cit-CQD on dopaminergic neurons within roundworms modified such that their dopaminergic neurons generated a green fluorescent color. A loss of fluorescence indicated neuronal loss.

Exposure to paraquat alone led to a 75% loss in fluorescence compared to the unexposed control. Pre-treatment with Cit-CQDs prevented the loss of dopaminergic neurons.

“We concluded that all concentrations of Cit-CQDs exhibited significant neuroprotection,” the researchers wrote.

“Our research suggests that a class of carbon nanomaterials, specifically CQDs derived from citric acid, is protective against environmental toxicant-induced oxidative stress, neuronal death, and increased organismal mortality,” the team concluded.

“Consequently, Cit-CQDs and potentially other CQDs might serve as a valuable platform for the campaign against sporadic neurodegenerative disorders” like Parkinson’s.

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