Graphene quantum dots prevent alpha-synucleinopathy in Parkinson's disease

Abstract

While the emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) is strongly correlated to the accumulation of alpha-synuclein ({\alpha}-syn) aggregates, there has been no clinical success in anti-aggregation agents for the disease to date. Here we show that graphene quantum dots (GQDs) exhibit anti-amyloid activity via direct interaction with {\alpha}-syn. Employing biophysical, biochemical, and cell-based assays as well as molecular dynamics (MD) simulation, we find that GQDs have notable potency in not only inhibiting fibrillization of {\alpha}-syn but also disaggregating mature fibrils in a time-dependent manner. Remarkably, GQDs rescue neuronal death and synaptic loss, reduce Lewy body (LB)/Lewy neurite (LN) formation, ameliorate mitochondrial dysfunctions, and prevent neuron-to-neuron transmission of {\alpha}-syn pathology induced by {\alpha}-syn preformed fibrils (PFFs) in neurons. In addition, in vivo administration of GQDs protects against {\alpha}-syn PFFs-induced loss of dopamine neurons, LB/LN pathology, and behavioural deficits through the penetration of the blood-brain barrier (BBB). The finding that GQDs function as an anti-aggregation agent provides a promising novel therapeutic target for the treatment of PD and related {\alpha}-synucleinopathies.