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Nat. Nanotechnol., Published 09 July 2018 | https://doi.org/10.1038/s41565-018-0179-y Graphene quantum dots prevent α-synucleinopathy in Parkinson’s disease

Donghoon Kim^1,2,12, Je Min Yoo^3,12, Heehong Hwang^1,4, Junghee Lee⁵, Su Hyun Lee^1,2, Seung Pil Yun^1,2,6, Myung Jin Park³, MinJun Lee ³, Seulah Choi¹, Sang Ho Kwon¹, Saebom Lee^1,2, Seung-Hwan Kwon^1,2, Sangjune Kim^1,2, Yong Joo Park⁷, Misaki Kinoshita⁸, Young-Ho Lee⁸, Seokmin Shin³, Seung R. Paik⁹, Sung Joong Lee⁴, Seulki Lee^7,10, Byung Hee Hong^3,5* and Han Seok Ko^1,2,6,11*

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

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

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

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

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

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

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

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

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

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

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

¹²These authors contributed equally: Donghoon Kim, Je Min Yoo.

^*Correspondence to Byung Hee Hong or Han Seok Ko

Abstract

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

논문정보

형식Research article
게재일2018년 07월 (BRIC 등록일 2018-07-13)
연구진국내(교신)+국외 연구진
분야 생명과학 > 신경생물학

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