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

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Abstract

Though emerging evidence indicates that the pathogenesis of Parkinson’s disease is strongly correlated to the accumulation1,2 and transmission3,4 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 fibrils5,6. 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.

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Fig. 1: Effect of GQDs on α-syn fibrillization and fibril disaggregation.
Fig. 2: Detailed analysis of the interaction between GQDs and mature α-syn fibrils during the dissociation process.
Fig. 3: Effect of GQDs on α-syn PFF-induced neuronal death, pathology and transmission in vitro.
Fig. 4: Effect of GQDs on α-syn-induced pathologies in vivo.

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Acknowledgements

This work was supported by BIOGRAPHENE Inc. and an NRF (National Research Foundation of Korea) grant funded by the Korean government (NRF-2014H1A2A1016534-Global PhD Fellowship Program, NRF-2011-357-C00119) and grants from NIH/NINDS NS082205, NIH/NINDS NS098006 and NIH/NINDS NS38377 from the Morris K. Udall Parkinson’s Disease Research Center. This work was made possible by support from the Johns Hopkins Medicine Discovery Fund. The authors acknowledge joint participation by the Diana Helis Henry Medical Research Foundation and the Adrienne Helis Malvin Medical Research Foundation through direct engagement in the continuous active conduct of medical research in conjunction with The Johns Hopkins Hospital and the Johns Hopkins University School of Medicine and the Foundation’s Parkinson’s Disease Program H-1, H-2013 and M-2014. The authors extend their sincere gratitude to H. Lee of Ewha Womans University for discussions and helpful advice.

Author information

B.H.H. and H.S.K. supervised the project. B.H.H. and J.M.Y. conceived the original idea of using GQDs for Parkinson’s disease. B.H.H., H.S.K., D.K. and J.M.Y. contributed to the study design. D.K., J.M.Y., H.H., S.H.L., S.P.Y., M.J.P., S.C., S.H.K., S.L., S.-H.K., S.K., Y.J.P., S.J.L. and S.L. contributed to overall data collection and interpretation. J.L., M.K., Y.-H.L. and S.R.P. contributed to NMR data collection and interpretation. M.L. and S.S. contributed to MD simulation and analysis. J.M.Y., J.L., S.R.P. and B.H.H. contributed to CD measurements and analysis. D.K., J.M.Y., S.H.L., B.H.H. and H.S.K wrote the paper. All authors discussed and commented on the manuscript.

Correspondence to Byung Hee Hong or Han Seok Ko.

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Supplementary Methods, Supplementary Table 1, Supplementary Figures 1–13, Supplementary References

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Kim, D., Yoo, J.M., Hwang, H. et al. Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease. Nature Nanotech 13, 812–818 (2018) doi:10.1038/s41565-018-0179-y

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