تقرير
Graphene quantum dots prevent alpha-synucleinopathy in Parkinson's disease
| العنوان: | Graphene quantum dots prevent alpha-synucleinopathy in Parkinson's disease |
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| المؤلفون: | Kim, Donghoon, Yoo, Je Min, Hwang, Heehong, Lee, Junghee, Lee, Su Hyun, Yun, Seung Pil, Park, Myung Jin, Lee, MinJun, Choi, Seulah, Kwon, Sang Ho, Lee, Saebom, Kwon, Seung-Hwan, Kim, Sangjune, Park, Yong Joo, Kinoshita, Misaki, Lee, Young-Ho, Shin, Seokmin, Paik, Seung R., Lee, Sung Joong, Lee, Seulki, Hong, Byung Hee, Ko, Han Seok |
| سنة النشر: | 2017 |
| المجموعة: | Condensed Matter Physics (Other) |
| مصطلحات موضوعية: | Physics - Medical Physics, Condensed Matter - Materials Science, Physics - Biological Physics |
| الوصف: | While the emerging evidence indicates that the pathogenesis of Parkinson's disease (PD) is strongly correlated to the accumulation of alpha-synuclein ({\alpha}-syn) aggregates, there has been no clinical success in anti-aggregation agents for the disease to date. Here we show that graphene quantum dots (GQDs) exhibit anti-amyloid activity via direct interaction with {\alpha}-syn. Employing biophysical, biochemical, and cell-based assays as well as molecular dynamics (MD) simulation, we find that GQDs have notable potency in not only inhibiting fibrillization of {\alpha}-syn but also disaggregating mature fibrils in a time-dependent manner. Remarkably, GQDs rescue neuronal death and synaptic loss, reduce Lewy body (LB)/Lewy neurite (LN) formation, ameliorate mitochondrial dysfunctions, and prevent neuron-to-neuron transmission of {\alpha}-syn pathology induced by {\alpha}-syn preformed fibrils (PFFs) in neurons. In addition, in vivo administration of GQDs protects against {\alpha}-syn PFFs-induced loss of dopamine neurons, LB/LN pathology, and behavioural deficits through the penetration of the blood-brain barrier (BBB). The finding that GQDs function as an anti-aggregation agent provides a promising novel therapeutic target for the treatment of PD and related {\alpha}-synucleinopathies. |
| نوع الوثيقة: | Working Paper |
| DOI: | 10.1038/s41565-018-0179-y |
| URL الوصول: | http://arxiv.org/abs/1710.07213 |
| رقم الأكسشن: | edsarx.1710.07213 |
| قاعدة البيانات: | arXiv |
| DOI: | 10.1038/s41565-018-0179-y |
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