Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease

Abstract

Though emerging evidence indicates that the pathogenesis of Parkinson's disease is strongly correlated to the accumulation and transmission of α-synuclein (α-syn) aggregates in the midbrain, no anti-aggregation agents have been successful at treating the disease in the clinic. Here, we show that graphene quantum dots (GQDs) inhibit fibrillization of α-syn and interact directly with mature fibrils, triggering their disaggregation. Moreover, GQDs can rescue neuronal death and synaptic loss, reduce Lewy body and Lewy neurite formation, ameliorate mitochondrial dysfunctions, and prevent neuron-to-neuron transmission of α-syn pathology provoked by α-syn preformed fibrils. We observe, in vivo, that GQDs penetrate the blood-brain barrier and protect against dopamine neuron loss induced by α-syn preformed fibrils, Lewy body/Lewy neurite pathology and behavioural deficits.

Complement and coagulation cascades are potentially involved in dopaminergic neurodegeneration in α-synuclein-based mouse models of Parkinson’s disease

“…The p-α-synuclein pathologies and propagation were also detected in the various regions including the SN after 6 months of αsynuclein PFFs injection ( Fig. 2F and G) as previously described (8,19,22,23,30).…”

“…Recombinant mouse -synuclein proteins were purified as previously described with IPTG independent inducible pRK172 vector system (19)(20)(21)(22)(23). Briefly, bacteria were harvested by centrifugation at 6,000 x g for 10 min after 16 h incubation at 37C.…”

“…To dissect pathways implicated in the pathogenesis of α-synuclein PFFs-induced mouse model of PD, the model was generated by injecting either PFF or PBS to the striatum via stereotactically unilateral injection as previously reported (8,19,22,23,30) (Fig. 2A).…”

Quantum effects in the brain: A review

“…They have also been used to model the mechanism by which anti-acetylcholine receptor antibodies contribute to the neuromuscular disorder myasthenia gravis 210 . Even more recently, graphene quantum dots have been shown to prevent and even undo the protein clumping of neurons in the brain that leads to Parkinson's disease 211 . A separate study study demonstrated similar results for Alzheimer's disease 212 .…”

Anti-biofilm Activity of Graphene Quantum Dots via Self-Assembly with Bacterial Amyloid Proteins

“…Recently this functionality was confirmed by observation of GQDs acting as inhibitors of fibrillation of the protein characteristic for Alzheimer's and Parkinson's disease. [28][29][30][31] Counteracting known problems of other anti-biofilm agents mentioned above, GQDs have high molecular weight (10 3 to 10 5 g/mol) that slows diffusion and are resistant to proteolytic degradation.…”