Nanomedicine-based Modulation of Parkinson's Disease Pathology Through Integrated Biological and Computational Approaches
Abstract
Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopamine-producing neurons and the aggregation of α-synuclein, a protein that misfolds into neurotoxic fibrils. Current therapies primarily alleviate motor symptoms but do not slow disease progression, leaving PD pathology unaddressed. Biocompatible nanoparticles, known as carbon nanodots (CNDs), represent a promising therapeutic approach by penetrating the blood-brain barrier (BBB) and distrupting amyloid structures. Preclinical studies in zebrafish models of neurodegeneration have shown that our CNDs, developed by the LeBlanc Lab, reduce tau and amyloid-β aggregation, decrease neuroinflammation, and improve neuronal function, emphasizing their translational potential for PD. Here, we demonstrate that CNDs inhibit aggregation in a dose-dependent manner in vitro, with certain variations showing strong inhibition at higher concentrations. We also show preliminary data on the impact of novel CNDs in a C. elegans model of α-synuclein aggregation. Our findings suggest that CNDs may interfere with α-synuclein misfolding, directly targeting a central process in PD. Beyond their direct therapeutic actions, CNDs can act as nanocarriers to enhance delivery of neuroprotective agents. Glucagon-like peptide-1 (GLP-1) receptor agonists, like exenatide, have shown promise in reducing oxidative stress and inflammation but are limited by poor BBB penetration. Hybridization with CNDs may overcome this limitation while simultaneously disrupting α-synuclein aggregation. Computational pre-screening with AlphaFold further supports our approach by modeling interactions between nanomedicines, GLP-1 receptors, and α-synuclein aggregates. Together, the evidence suggests that CNDs act as both direct inhibitors of protein misfolding and drug-delivery vehicles, offering a disease-modifying approach for PD.
Faculty Sponsors
Dr. Akshay Naraine, Dr. Eduardo Veliz, Dr. Roger LeBlanc, Dr. Per Svenningsson
Project Type
Event
Location
Alvin Sherman Library
Start Date
1-4-2026 2:19 PM
End Date
2-4-2026 12:00 PM
Nanomedicine-based Modulation of Parkinson's Disease Pathology Through Integrated Biological and Computational Approaches
Alvin Sherman Library
Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopamine-producing neurons and the aggregation of α-synuclein, a protein that misfolds into neurotoxic fibrils. Current therapies primarily alleviate motor symptoms but do not slow disease progression, leaving PD pathology unaddressed. Biocompatible nanoparticles, known as carbon nanodots (CNDs), represent a promising therapeutic approach by penetrating the blood-brain barrier (BBB) and distrupting amyloid structures. Preclinical studies in zebrafish models of neurodegeneration have shown that our CNDs, developed by the LeBlanc Lab, reduce tau and amyloid-β aggregation, decrease neuroinflammation, and improve neuronal function, emphasizing their translational potential for PD. Here, we demonstrate that CNDs inhibit aggregation in a dose-dependent manner in vitro, with certain variations showing strong inhibition at higher concentrations. We also show preliminary data on the impact of novel CNDs in a C. elegans model of α-synuclein aggregation. Our findings suggest that CNDs may interfere with α-synuclein misfolding, directly targeting a central process in PD. Beyond their direct therapeutic actions, CNDs can act as nanocarriers to enhance delivery of neuroprotective agents. Glucagon-like peptide-1 (GLP-1) receptor agonists, like exenatide, have shown promise in reducing oxidative stress and inflammation but are limited by poor BBB penetration. Hybridization with CNDs may overcome this limitation while simultaneously disrupting α-synuclein aggregation. Computational pre-screening with AlphaFold further supports our approach by modeling interactions between nanomedicines, GLP-1 receptors, and α-synuclein aggregates. Together, the evidence suggests that CNDs act as both direct inhibitors of protein misfolding and drug-delivery vehicles, offering a disease-modifying approach for PD.
Comments
Dr. Eduardo Veliz and Dr. Roger LeBlanc: University of Miami; Dr. Per Svenningsson: Karolinska Institute; Dr. Akshay Naraine: Nova Southeastern University