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Updated: May 10, 2025
Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease
Published on: January 7, 2014
Development of novel carbon-based biomedical platforms for intervention in xenotoxicant-induced Parkinson's disease
Jyotish Kumar1, Armando Varela-Ramirez2, Mahesh Narayan1
1Department of Chemistry and Biochemistry, The University of Texas at El Paso (UTEP), El Paso, USA.
Abstract:
Chronic exposure to herbicides, weedicides, and pesticides is associated with the onset and progress of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic Lateral Sclerosis (ALS). Here, we have investigated whether quinic- and chlorogenic-acid-derived Carbon Quantum Dots (QACQDs and ChACQDs, respectively) protect against a (pesticide) paraquat-insult model of PD. Our results indicated that both types of CQDs intervened in the soluble-to-toxic transformation of the amyloid-forming model protein Hen Egg White Lysozyme (HEWL). Furthermore, QACQDs and ChACQDs demonstrated antioxidant activity while remaining biocompatible in a human neuroblastoma-derived cell line (SH-SY5Y) up to 5 mg/ml and protected the cell line from the environmental neurotoxicant (paraquat). Importantly, both CQDs were found to protect dopaminergic neuronal ablation in a paraquat model of Parkinson's disease using the nematode C. elegans. Our results are significant because both plant-derived organic acids cross the blood-brain barrier, making them attractive for developing CQD architectures. Furthermore, since the synthesis of these CQDs was performed using green chemistry methods from precursor acids that cross the BBB, these engineered bionanomaterial platforms are tantalizing candidates for preventing neurodegenerative disorders associated with exposure to environmental neurotoxicants.
Insights
Green-synthesized carbon quantum dots derived from plant acids protect against pesticide-induced neurodegeneration. These biocompatible nanomaterials show promise for preventing Parkinson
Area of Science:
- Nanomaterials Science
- Neuroscience
- Biochemistry
Background:
- Chronic exposure to pesticides is linked to neurodegenerative diseases like Parkinson's disease (PD).
- Environmental neurotoxicants, such as paraquat, are implicated in PD pathogenesis.
- Developing effective neuroprotective agents is crucial for combating neurodegenerative disorders.
Purpose of the Study:
- To investigate the neuroprotective potential of quinic- and chlorogenic-acid-derived Carbon Quantum Dots (QACQDs and ChACQDs) against paraquat-induced neurotoxicity.
- To evaluate the ability of QACQDs and ChACQDs to prevent the aggregation of amyloid-forming proteins.
- To assess the biocompatibility and efficacy of these CQDs in cellular and model organisms.
Main Methods:
- Synthesis of QACQDs and ChACQDs using green chemistry methods.
- In vitro studies using Hen Egg White Lysozyme (HEWL) to assess protein aggregation inhibition.
- In vitro studies using human neuroblastoma cells (SH-SY5Y) to evaluate biocompatibility and protection against paraquat.
- In vivo studies using the nematode *C. elegans* as a model for paraquat-induced dopaminergic neurodegeneration.
Main Results:
- QACQDs and ChACQDs inhibited the transformation of HEWL into toxic aggregates.
- Both CQDs exhibited antioxidant activity and were biocompatible with SH-SY5Y cells up to 5 mg/ml.
- QACQDs and ChACQDs protected SH-SY5Y cells from paraquat-induced toxicity.
- CQDs demonstrated neuroprotection against paraquat in a *C. elegans* model of Parkinson's disease.
Conclusions:
- Plant-derived QACQDs and ChACQDs possess significant neuroprotective properties against pesticide-induced damage.
- These CQDs are biocompatible and can inhibit protein aggregation, key factors in neurodegenerative diseases.
- Their ability to cross the blood-brain barrier makes them promising candidates for developing novel therapeutic strategies against neurodegenerative disorders.
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