机构:[a]Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120, China中山大学附属第二医院[b]Department of Neurology and Outpatient Department of Internal Medicine, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, 510120, China大德路总院内科广东省中医院[c]School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, China[d]Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China中山大学附属第二医院[e]Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China[f]Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China中山大学附属第二医院[g]Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
Alzheimer disease (AD) is a neurodegenerative disorder and the most common form of dementia. Histopathologically is characterized by the presence extracellular neuritic plaques and with a large number of neurons lost. In this paper, we design a new nanomaterial, graphene quantum dots (GQDs) conjugated neuroprotective peptide glycine-proline-glutamate (GQDG) and administer it to APP/PS1 transgenic mice. The in vitro assays including ThT and CD proved that GQDs and GQDG could inhibit the aggregation of A beta(1-42) fibrils. Morris water maze was performed to exanimate learning and memory capacity of APP/PS1 transgenic mice. The surface area of A beta plaque deposits reduced in the GQDG group compared to the Tg Ctrl groups. Furthermore, newly generated neuronal precursor cell and neuron were test by immunohistochemical. Besides, neurons were impregnated by Dil using gene gun to show dendritic spine. Results indicated enhancement of learning and memory capacity and increased amounts of dendritic spine were observed. Inflammation factors and amyloid-beta (A beta) were tested with suspension array and ELISA, respectively. Several pro-inflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-33, IL-17 alpha, MIP-1 beta and TNF-alpha) had decreased in GQDG group compared with Control group. Reversely, anti-inflammatory cytokines (IL-4, IL-10) had increased in GQDG group compared with Control group. Thus, we demonstrate that the GQDG is a promising drug in treatment of neurodegenerative diseases such as AD. (C) 2016 Elsevier Ltd. All rights reserved.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81372919, 51303064]; Guangdong Natural Science FoundationNational Natural Science Foundation of Guangdong Province [2014A030313016]; Science and Technology Planning Fundamental Research Project of Shenzhen [JCYJ20150324140036853]
第一作者机构:[a]Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120, China
共同第一作者:
通讯作者:
通讯机构:[a]Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120, China[e]Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China[f]Laboratory of RNA and Major Diseases of Brain and Heart, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China[g]Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China[*1]Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou 510632, China.[*2]Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yanjiang West Road, Guangzhou, 510120, China.