Abstrakt

Synucleinopathies, including Parkinson’s disease and multiple system atrophy (MSA), areneurodegenerative disorders characterized by aggregation of α-synuclein (ASN).Nanomaterials capable of modulating protein misfolding represent a potential interventionstrategy. Here, we synthesized graphene quantum dots (GQDs) and systematically evaluatedtheir physicochemical properties and biological activity against ASN aggregation. The GQDswere characterized using spectroscopic, electron microscopy, and colloidal techniques todetermine surface chemistry, charge, optical properties, and crystalline structure. Biologicalevaluation demonstrated cytocompatibility in human dermal fibroblasts (IC50 = 90 µg mL−1 at24 h) with assessments of DNA damage and inflammatory responses. Functionally, GQDsdestabilized preformed ASN fibrils in a cell-free assay, as evidenced by reduced Thioflavin-Tfluorescence. In primary murine dopaminergic neurons, GQDs decrease pS129-ASN inclusionformation without compromising neuronal viability. Most importantly, intranasal administra-tion of GQDs in an MSA mouse model reduced ASN immunoreactivity in the brain. Collectively,our data indicate that the synthetized GQDs are bioactive and can modulate ASN aggregationacross cell-free, neuronal, and in vivo models. Importantly, physicochemical properties governnano – bio interactions, providing a rationale for further refinement of GQDs as a biomaterialplatform for synucleinopathy-related applications.