P3.12. NANOMATERIAL-BASED STRATEGIES AGAINST PARKINSON’S-RELATED Α-SYNUCLEIN MISFOLDING AND AGGREGATION
Anna Alwani1, Oliwia Kowalska2, Magdalena Oćwieja2, Piotr Chmielarz1
1 Maj Institute of Pharmacology, Polish Academy of Sciences, Department of Brain Biochemistry, Kraków, Poland
2 Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Department of Colloid and Interface Physicochemistry, Kraków, Poland
INTRODUCTION: α-Synucleinopathy is a well-recognized hallmark of several neurodegenerative disorders, including Parkinson’s disease. Aggregates of α-synuclein spread into different neuronal populations during disease progression, which putatively contributes to a broad spectrum of symptoms such as sleep disturbances, motor dysfunction, depression, cognitive impairment, and others. In recent years, nanotechnology has emerged as a promising field for both the diagnosis and treatment of proteinopaties. In particular, Graphene Quantum Dots (GQDs) and Gold Nanoparticles (AuNPs) have shown potential in interfering with the fibrillization process of α-synuclein.
AIM(S): The primary aim of this study was to investigate the impact of these nanoparticles on α-synuclein aggregation using in vitro neuronal model of α-synucleinopathy.
METHOD(S): Graphene- or gold-based nanoparticles were administered to mice primary neuronal cultures (cortical, hippocampal, dopaminergic) on day 7, one hour after treatment with preformed fibrils (PFFs) of mouse recombinant α-synuclein. The cultures were then incubated for 7 days. After fixation with 4% PFA, the cells were stained using primary antibodies (NeuN, TH, and α-synuclein phospho-S129) and corresponding secondary antibodies (Alexa Fluor 488 and 647).
RESULTS: GQDs, applied at concentrations of 5 µg/mL and 10 µg/mL, effectively reduced the proportion of cells exhibiting pathological α-synuclein accumulation across all three types of neuronal cultures, without exerting any negative effects on neuronal survival. Similarly, AuNPs at 50 µg/mL demonstrated a comparable protective effect, which was observed in hippocampal and cortical neuronal cultures, also without compromising cell viability.
CONCLUSIONS: These findings indicate that GQDs and AuNPs can reduce pathological α-synuclein accumulation without affecting neuronal viability, supporting their potential as therapeutic agents in synucleinopathies.
FINANCIAL SUPPORT: Supported by NCN, grant number 2021/42/E/NZ7/00246 (Sonata BIS 11).