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

Nature Nanotechnology volume 13, pages 812–818 (2018)Cite this article

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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.

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Author notes

  1. These authors contributed equally: Donghoon Kim, Je Min Yoo.

Authors and Affiliations

  1. Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Donghoon Kim, Heehong Hwang, Su Hyun Lee, Seung Pil Yun, Seulah Choi, Sang Ho Kwon, Saebom Lee, Seung-Hwan Kwon, Sangjune Kim & Han Seok Ko

  2. Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Donghoon Kim, Su Hyun Lee, Seung Pil Yun, Saebom Lee, Seung-Hwan Kwon, Sangjune Kim & Han Seok Ko

  3. Department of Chemistry, College of Natural Science, Seoul National University, Seoul, Republic of Korea

    Je Min Yoo, Myung Jin Park, MinJun Lee, Seokmin Shin & Byung Hee Hong

  4. Department of Neuroscience and Physiology, Interdisciplinary Program in Neuroscience, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea

    Heehong Hwang & Sung Joong Lee

  5. Inter-University Semiconductor Research Centre, Seoul National University, Seoul, Republic of Korea

    Junghee Lee & Byung Hee Hong

  6. Adrienne Helis Malvin Medical Research Foundation, New Orleans, LA, USA

    Seung Pil Yun & Han Seok Ko

  7. The Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Yong Joo Park & Seulki Lee

  8. Institute for Protein Research, Osaka University, Yamadaoka, Osaka, Japan

    Misaki Kinoshita & Young-Ho Lee

  9. School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Seoul, Republic of Korea

    Seung R. Paik

  10. The Centre for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Seulki Lee

  11. Diana Helis Henry Medical Research Foundation, New Orleans, LA, USA

    Han Seok Ko

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  1. Donghoon Kim
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Contributions

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.

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Correspondence to Byung Hee Hong or Han Seok Ko.

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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). https://doi.org/10.1038/s41565-018-0179-y

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