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

TL;DR

Graphene quantum dots (GQDs) can inhibit alpha-synuclein aggregation, disaggregate existing fibrils, and protect neurons in Parkinson's disease models, offering a promising new therapeutic approach.

Contribution

This study demonstrates for the first time that GQDs directly interact with alpha-synuclein to prevent and reverse fibril formation, showing therapeutic potential in PD.

Findings

GQDs inhibit alpha-synuclein fibrillization

GQDs disaggregate mature fibrils

GQDs protect neurons and improve behavioral deficits in vivo

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.