Quantum dots made from the carbon material graphene prevent alpha-synuclein from aggregating into strand-like structures known as fibrils. They also help disaggregate fibrils that have already formed. Alpha-synuclein fibrils are thought to be implicated in Parkinson’s disease because they kill dopamine-generating neurons, so the new findings might help in the development of therapies to treat this disease as well as others in which fibrilization occurs.
Synucleins are a family of proteins typically found in neural tissue. Researchers believe that one type of synuclein, alpha-synuclein, twists into fibrils, which then accumulate in the midbrain of patients with Parkinson’s. Treatments with efficient anti-aggregation agents might thus be one way of fighting the disease.
A team led by Byung Hee Hong of Seoul National University and Han Seok Ko of The Johns Hopkins University in Baltimore have now found that graphene quantum dots (GQDs) bind to alpha-synuclein in vitro. Thanks to fluorescence and turbidity assays, as well as transmission electron microscopy measurements, the researchers found that the dots prevent alpha-synuclein from forming into fibrils. The nanostructures also dissociate already-formed fibrils into short fragments, with the average length of the fragments shortening from 1 micron to 235 nm and 70 nm after 6 and 24 hours respectively. The number of fragments starts to decrease after three days too and cannot be detected at all after seven days, which implies that the fibrils completely disintegrate after this time.
Mice show improved symptoms of the disease after six months
In their experiments, Hong and Ko’s team also injected the GQDs into the bloodstream of transgenic mice with Parkinson’s and found that they showed improved symptoms of the disease after six months – as assessed by routine cylinder and pole tests. The mice showed fewer movement problems, were able to use both forepaws to balance themselves on cylinders and ran down poles quicker. The researchers say that these improvements could come from the fact that the quantum dots are small enough to penetrate the blood-brain barrier and protect against dopamine neuron loss induced by alpha-synuclein preformed fibrils.
The GQDs do not show any appreciable in vitro and in vivo toxicity after six months of “prolonged injection” either and can be cleared from the body and excreted into urine, they add. The quantum dots might produce a similar effect in other diseases in which fibrilization occurs. Indeed, previous research by another team has already shown that injecting them into mice with Alzheimer’s inhibits the fibrilization of beta-amyloid peptides.
Full details of the research have been published in Nature Nanotechnology 10.1038/s41565-018-0179-y.
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