Title: 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.