Graphene quantum dots prevent alpha-synucleinopathy in Parkinson's disease
Abstract
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.
Cite
@article{arxiv.1710.07213,
title = {Graphene quantum dots prevent alpha-synucleinopathy in Parkinson's disease},
author = {Donghoon Kim and Je Min Yoo and Heehong Hwang and Junghee Lee and Su Hyun Lee and Seung Pil Yun and Myung Jin Park and MinJun Lee and Seulah Choi and Sang Ho Kwon and Saebom Lee and Seung-Hwan Kwon and Sangjune Kim and Yong Joo Park and Misaki Kinoshita and Young-Ho Lee and Seokmin Shin and Seung R. Paik and Sung Joong Lee and Seulki Lee and Byung Hee Hong and Han Seok Ko},
journal= {arXiv preprint arXiv:1710.07213},
year = {2018}
}