Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Nanotechnol. 2018 Sep;13(9):812-818. doi: 10.1038/s41565-018-0179-y. Epub 2018 Jul 9.
Though emerging evidence indicates that the pathogenesis of Parkinson's disease is strongly correlated to the accumulation and transmission 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. 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.
尽管新出现的证据表明,帕金森病的发病机制与中脑α-突触核蛋白(α-syn)聚集体的积累和传播密切相关,但在临床上,没有一种抗聚集药物能成功治疗这种疾病。在这里,我们表明石墨烯量子点(GQDs)抑制α-syn 的纤维化,并与成熟的原纤维直接相互作用,引发其解聚。此外,GQDs 可以挽救神经元死亡和突触丢失,减少路易体和路易神经丝的形成,改善线粒体功能障碍,并防止由α-syn 预制纤维引起的α-syn 病理学的神经元到神经元的传递。我们在体内观察到,GQDs 穿透血脑屏障,防止由α-syn 预制纤维、路易体/路易神经丝病理和行为缺陷引起的多巴胺神经元丢失。
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