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تسجيل مستخدم جديدGraphene quantum dots prevent alpha-synucleinopathy in Parkinsons disease
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While the emerging evidence indicates that the pathogenesis of Parkinsons 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.
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