Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

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


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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others


  1. Dawson, T. M. & Dawson, V. L. Molecular pathways of neurodegeneration in Parkinson’s disease. Science 302, 819–822 (2003).

    Article  Google Scholar 

  2. Spillantini, M. G. et al. Alpha-synuclein in Lewy bodies. Nature 388, 839–840 (1997).

    Article  Google Scholar 

  3. Li, J. Y. et al. Lewy bodies in grafted neurons in subjects with Parkinson’s disease suggest host-to-graft disease propagation. Nat. Med. 14, 501–503 (2008).

    Article  Google Scholar 

  4. Desplats, P. et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc. Natl Acad. Sci. USA 106, 13010–13015 (2009).

    Article  Google Scholar 

  5. Volpicelli-Daley, L. A. et al. Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 72, 57–71 (2011).

    Article  Google Scholar 

  6. Luk, K. C. et al. Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338, 949–953 (2012).

    Article  Google Scholar 

  7. Varela, L., Bell, C. H., Armitage, J. P. & Redfield, C. 1H, 13C and 15N resonance assignments for the response regulator CheY3 from Rhodobacter sphaeroides. Biomol. NMR Assign. 10, 373–378 (2016).

    Article  Google Scholar 

  8. Bodner, C. R., Dobson, C. M. & Bax, A. Multiple tight phospholipid-binding modes of alpha-synuclein revealed by solution NMR spectroscopy. J. Mol. Biol. 390, 775–790 (2009).

    Article  Google Scholar 

  9. Tuttle, M. D. et al. Solid-state NMR structure of a pathogenic fibril of full-length human alpha-synuclein. Nat. Struct. Mol. Biol. 23, 409–415 (2016).

    Article  Google Scholar 

  10. Giasson, B. I., Murray, I. V. J., Trojanowski, J. Q. & Lee, V. M. Y. A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly. J. Biol. Chem. 276, 2380–2386 (2001).

    Article  Google Scholar 

  11. van Stokkum, I. H., Spoelder, H. J., Bloemendal, M., van Grondelle, R. & Groen, F. C. Estimation of protein secondary structure and error analysis from circular dichroism spectra. Anal. Biochem 191, 110–118 (1990).

    Article  Google Scholar 

  12. Sreerama, N. & Woody, R. W. Estimation of protein secondary structure from circular dichroism spectra: comparison of CONTIN, SELCON, and CDSSTR methods with an expanded reference set. Anal. Biochem. 287, 252–260 (2000).

    Article  Google Scholar 

  13. Lin, M. T. & Beal, M. F. Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443, 787–795 (2006).

    Article  Google Scholar 

  14. Czupalla, C. J., Liebner, S. & Devraj, K. In vitro models of the blood–brain barrier. Methods Mol. Biol. 1135, 415–437 (2014).

    Article  Google Scholar 

  15. Lee, M. K. et al. Human α-synuclein-harboring familial Parkinson’s disease-linked Ala-53→Thr mutation causes neurodegenerative disease with α-synuclein aggregation in transgenic mice. Proc. Natl Acad. Sci. USA 99, 8968–8973 (2002).

    Article  Google Scholar 

  16. Brahmachari, S. et al. Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration. J. Clin. Invest. 126, 2970–2988 (2016).

    Article  Google Scholar 

  17. Li, Q. et al. Modulating Aβ33–42 peptide assembly by graphene oxide. Chem. Eur. J. 20, 7236–7240 (2014).

    Article  Google Scholar 

  18. Mahmoudi, M., Akhavan, O., Ghavami, M., Rezaee, F. & Ghiasi, S. M. A. Graphene oxide strongly inhibits amyloid beta fibrillation. Nanoscale 4, 7322–7325 (2012).

    Article  Google Scholar 

  19. Liu, Y. et al. Graphene quantum dots for the inhibition of beta amyloid aggregation. Nanoscale 7, 19060–19065 (2015).

    Article  Google Scholar 

  20. Yang, Z. X. et al. Destruction of amyloid fibrils by graphene through penetration and extraction of peptides. Nanoscale 7, 18725–18737 (2015).

    Article  Google Scholar 

  21. Volpicelli-Daley, L. A., Luk, K. C. & Lee, V. M. Addition of exogenous alpha-synuclein preformed fibrils to primary neuronal cultures to seed recruitment of endogenous alpha-synuclein to Lewy body and Lewy neurite-like aggregates. Nat. Protoc. 9, 2135–2146 (2014).

    Article  Google Scholar 

  22. Delaglio, F. et al. NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 6, 277–293 (1995).

    Article  Google Scholar 

  23. Lee, W., Tonelli, M. & Markley, J. L. NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy. Bioinformatics 31, 1325–1327 (2015).

    Article  Google Scholar 

  24. Abraham, M. J. et al. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX 1-2, 19–25 (2015).

    Article  Google Scholar 

  25. Mackerell, A. D.Jr., Feig, M. & Brooks, C. L. III Extending the treatment of backbone energetics in protein force fields: limitations of gas-phase quantum mechanics in reproducing protein conformational distributions in molecular dynamics simulations. J. Comput. Chem. 25, 1400–1415 (2004).

    Article  Google Scholar 

  26. Yu, W., He, X., Vanommeslaeghe, K. & MacKerell, A. D. Jr. Extension of the CHARMM General Force Field to sulfonyl-containing compounds and its utility in biomolecular simulations. J. Comput. Chem. 33, 2451–2468 (2012).

    Article  Google Scholar 

  27. Lee, M. K. et al. Human α-synuclein-harboring familial Parkinson’s disease-linked Ala-53→Thr mutation causes neurodegenerative disease with α-synuclein aggregation in transgenic mice. Proc. Natl Acad. Sci. USA 99, 8968–8973 (2002).

    Article  Google Scholar 

  28. Peelaerts, W. et al. α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature 522, 340–344 (2015).

    Article  Google Scholar 

  29. Mao, X. et al. Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science 353, aah3374 (2016).

    Article  Google Scholar 

Download references


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

Authors and Affiliations



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.

Corresponding authors

Correspondence to Byung Hee Hong or Han Seok Ko.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Supplementary Information

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

Reporting Summary

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing