CoChat
Sign Up
Cited by 455Parkinson's Disease Mechanisms and TreatmentsGraphene and Nanomaterials ApplicationsAlzheimer's disease research and treatments

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

Open access
Kim, Donghoon, Yoo, Je Min, Hwang, Heehong, Lee, Junghee, Lee, Su Hyun, Yun, Seung Pil, Park, Myung Jin, Lee, MinJun +14 more·2018·Nature Nanotechnology
DOI 10.1038/s41565-018-0179-yPMC PMC6351226
Open this paper in CoChat — free account

Abstract

Though emerging evidence indicates that the pathogenesis of Parkinson's disease is strongly correlated to the accumulation 1,2 and transmission 3,4 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 fibrils 5,6. 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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41565-018-0179-y

Cites

3 of 3 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Graphene quantum dots at 2 to 4 nm have higher BBB permeability than graphene oxide at 5 to 20 nm.

    “Graphene quantum dots at a size range from 2 to 4 nm have higher BBB permeability than GO at a size from 5 to 20 nm”

    From The blood–brain barrier: Structure, regulation and drug delivery (2023) · cites this paper as [317]

    The comparison passage (section labeled Abstract; page unavailable) says that nano-GOs measuring approximately 5–20 nm have much lower BBB permeability than GQDs. Our copy does not establish the claimed 2–4 nm size range for GQDs, so that part of the sentence is unsupported. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 25

  1. [1]Dawson TM & Dawson VL Molecular pathways of neurodegeneration in Parkinson’s disease. Science 302, 819– 822 (2003). 14593166
  2. [2]Spillantini MG Alpha-synuclein in Lewy bodies. Nature 388, 839– 840 (1997). 9278044
  3. [4]Desplats P Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc. Natl Acad. Sci. USA 106, 13010– 13015 (2009). 19651612 PMC2722313
  4. [5]Volpicelli-Daley LA Exogenous alpha-synuclein fibrils induce Lewy body pathology leading to synaptic dysfunction and neuron death. Neuron 72, 57– 71 (2011). 21982369 PMC3204802
  5. [6]Luk KC Pathological alpha-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice. Science 338, 949– 953 (2012). 23161999 PMC3552321
  6. [7]Varela L, Bell CH, Armitage JP & Redfield C 1H, 13C and 15N resonance assignments for the response regulator CheY3 from Rhodobacter sphaeroides. Biomol. NMR Assign. 10, 373– 378 (2016). 27468962 PMC5039241
  7. [8]Bodner CR, Dobson CM & Bax A Multiple tight phospholipid-binding modes of alpha-synuclein revealed by solution NMR spectroscopy. J. Mol. Biol 390, 775– 790 (2009). 19481095 PMC2709488
  8. [9]Tuttle MD Solid-state NMR structure of a pathogenic fibril of full-length human alpha-synuclein. Nat. Struct. Mol. Biol 23, 409– 415 (2016). 27018801 PMC5034296
  9. [11]van Stokkum IH, Spoelder HJ, Bloemendal M, van Grondelle R & Groen FC Estimation of protein secondary structure and error analysis from circular dichroism spectra. Anal. Biochem 191, 110– 118 (1990). 2077933
  10. [12]Sreerama N & Woody RW 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). 11112271
  11. [14]Czupalla CJ, Liebner S & Devraj K In vitro models of the blood–brain barrier. Methods Mol. Biol 1135, 415– 437 (2014). 24510883
  12. [15]Lee MK 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). 12084935 PMC124407
  13. [16]Brahmachari S Activation of tyrosine kinase c-Abl contributes to α-synuclein-induced neurodegeneration. J. Clin. Invest 126, 2970– 2988 (2016). 27348587 PMC4966315
  14. [17]Li Q Modulating Aβ33–42 peptide assembly by graphene oxide. Chem. Eur. J 20, 7236– 7240 (2014). 24838837
  15. [18]Mahmoudi M, Akhavan O, Ghavami M, Rezaee F & Ghiasi SMA Graphene oxide strongly inhibits amyloid beta fibrillation. Nanoscale 4, 7322– 7325 (2012). 23079862
  16. [19]Liu Y Graphene quantum dots for the inhibition of beta amyloid aggregation. Nanoscale 7, 19060– 19065 (2015). 26515666
  17. [20]Yang ZX Destruction of amyloid fibrils by graphene through penetration and extraction of peptides. Nanoscale 7, 18725– 18737 (2015). 26503908
  18. [21]Volpicelli-Daley LA, Luk KC & Lee VM 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). 25122523 PMC4372899
  19. [22]Delaglio F NMRPipe: a multidimensional spectral processing system based on UNIX pipes. J. Biomol. NMR 6, 277– 293 (1995). 8520220
  20. [23]Lee W, Tonelli M & Markley JL NMRFAM-SPARKY: enhanced software for biomolecular NMR spectroscopy. Bioinformatics 31, 1325– 1327 (2015). 25505092 PMC4393527
  21. [25]Mackerell AD Jr., Feig M & Brooks CL 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). 15185334
  22. [26]Yu W, He X, Vanommeslaeghe K & MacKerell AD 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). 22821581 PMC3477297
  23. [27]Lee MK 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). 12084935 PMC124407
  24. [28]Peelaerts W α-Synuclein strains cause distinct synucleinopathies after local and systemic administration. Nature 522, 340– 344 (2015). 26061766
  25. [29]Mao X Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. Science 353, aah3374 (2016). 27708076 PMC5510615

Cited by

Sorted by citations

Authors
Kim, D., Yoo, J. M., Hwang, H., Lee, J., Lee, S. H., Yun, S. P., Park, M. J., Lee, M., Choi, S., Kwon, S. H., Lee, S., Kwon, S.-H., Kim, S., Park, Y. J., Kinoshita, M., Lee, Y.-H., Shin, S., Paik, S. R., Lee, S. J., Lee, S., Hong, B. H., & Ko, H. S.
Affiliations
  • Johns Hopkins University (US)
  • Seoul National University (KR)
  • Institute for Protein Research, The University of Osaka (JP)
Corresponding author
  • Hong, Byung Hee
  • Ko, Han Seok
ORCID
Venue
Nature Nanotechnology
Publisher
Springer Science and Business Media LLC
Published
2018-07-09
Volume
13
Issue
9
Pages
812-818
ISSN
  • 1748-3387 (ISSN-L)
  • 1748-3395
DOI
10.1038/s41565-018-0179-y
PMC
PMC6351226
OpenAlex
W2857430289
Cited by
455
References
3
Citations by year
2026: 24 · 2025: 58 · 2024: 50 · 2023: 70 · 2022: 74 · 2021: 80 · 2020: 61 · 2019: 31 · 2018: 7
FWCI
30.39
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Nanotechnology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • arXiv (Cornell University) (submittedVersion)
  • Seoul National University Open Repository (Seoul National University) (submittedVersion)
  • arXiv (Cornell University)
Funders
  • Japan Society for the Promotion of Science (17K07362)
  • National Institute of Neurological Disorders and Stroke (R21NS098006, R01NS082205, P50NS038377)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Physical Sciences › Engineering › Biomedical Engineering › Graphene and Nanomaterials Applications
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
graphene quantum dots, alpha-synuclein, Parkinson's disease, Lewy bodies, Lewy neurites, mitochondrial dysfunction, dopamine neuron loss, neuroprotection, blood-brain barrier penetration, neurotoxicity
MeSH terms
Animals, Blood-Brain Barrier, Cells, Cultured, Graphite, Humans, Parkinson Disease, Synapses, Lewy Bodies, Quantum Dots, Mice, alpha-Synuclein, Protein Aggregation, Pathological

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review