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

Nat Nanotechnol. 2018 Sep;13(9):812-818. doi: 10.1038/s41565-018-0179-y. Epub 2018 Jul 9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism*
  • Blood-Brain Barrier / pathology
  • Cells, Cultured
  • Graphite* / chemistry
  • Graphite* / pharmacokinetics
  • Graphite* / pharmacology
  • Humans
  • Lewy Bodies / metabolism
  • Lewy Bodies / pathology
  • Mice
  • Parkinson Disease / metabolism
  • Parkinson Disease / pathology
  • Parkinson Disease / prevention & control*
  • Protein Aggregation, Pathological / metabolism
  • Protein Aggregation, Pathological / pathology
  • Protein Aggregation, Pathological / prevention & control*
  • Quantum Dots* / chemistry
  • Synapses / metabolism
  • Synapses / pathology
  • alpha-Synuclein / metabolism*

Substances

  • Snca protein, mouse
  • alpha-Synuclein
  • Graphite