Abstract
Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone primarily produced in the gut and brainstem. GLP-1 helps regulate glucose levels and appetite control, but recent evidence suggests that it may play a critical role in neurodegenerative diseases. GLP-1 receptors, part of the G-protein-coupled receptor family, activate intracellular metabolic and neurological signal cascades mainly via activation, or agonism. GLP-1 agonists, a drug class which includes Ozempic, were initially developed to manage type 2 diabetes, but recent studies have demonstrated neuroprotective properties for GLP-1 agonists in Alzheimer’s and Parkinson’s disease (PD) models, thereby broadening their potential therapeutic applications. While early clinical trials for PD demonstrated efficacy of GLP-1 agonists by showing improved motor function and cognitive health, the recent Phase III trial in the UK for PD failed. One reason for this may be GLP-1 agonists’ inability to cross the blood-brain barrier (BBB). GLP-1 agonists were designed to stay in the periphery, so we hypothesize that nanomedicine technology can overcome this hurdle and produce synergistic, therapeutic effects. Using carbon nanodots, a biocompatible nanotechnology, we aim to achieve linkage with GLP-1 agonists, increase BBB permeability, and disrupt harmful protein aggregates to provide increased neuroprotection and bioavailability. Here, we show preliminary findings of novel carbon nanodots disrupting harmful, alpha-synuclein aggregation and computational modeling using the 2024 Nobel Prize winning program, AlphaFold2.
Faculty Sponsors
Dr. Per Svenningsson, Dr. Akshay Naraine
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-2-2025 12:45 PM
End Date
4-3-2025 12:00 AM
Investigating Efficacy of Nanomedicine for Novel Parkinson's Disease Therapeutics
Alvin Sherman Library
Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone primarily produced in the gut and brainstem. GLP-1 helps regulate glucose levels and appetite control, but recent evidence suggests that it may play a critical role in neurodegenerative diseases. GLP-1 receptors, part of the G-protein-coupled receptor family, activate intracellular metabolic and neurological signal cascades mainly via activation, or agonism. GLP-1 agonists, a drug class which includes Ozempic, were initially developed to manage type 2 diabetes, but recent studies have demonstrated neuroprotective properties for GLP-1 agonists in Alzheimer’s and Parkinson’s disease (PD) models, thereby broadening their potential therapeutic applications. While early clinical trials for PD demonstrated efficacy of GLP-1 agonists by showing improved motor function and cognitive health, the recent Phase III trial in the UK for PD failed. One reason for this may be GLP-1 agonists’ inability to cross the blood-brain barrier (BBB). GLP-1 agonists were designed to stay in the periphery, so we hypothesize that nanomedicine technology can overcome this hurdle and produce synergistic, therapeutic effects. Using carbon nanodots, a biocompatible nanotechnology, we aim to achieve linkage with GLP-1 agonists, increase BBB permeability, and disrupt harmful protein aggregates to provide increased neuroprotection and bioavailability. Here, we show preliminary findings of novel carbon nanodots disrupting harmful, alpha-synuclein aggregation and computational modeling using the 2024 Nobel Prize winning program, AlphaFold2.
Comments
Dr. Eduardo Veliz & Dr. Roger LeBlac: University of Miami, Per Svenningsson: Karolinska Institute