机构：[1]National Pharmaceutical Engineering Center for Solid Preparation inChinese Herbal Medicine, Jiangxi University of Traditional ChineseMedicine, Nanchang 330006, China[2]Guangdong Provincial Key Laboratory of New Drug Design andEvaluation, Shenzhen University Health Science Center,Shenzhen 518060, China[3]Jiangxi Provincial Children’s Hospital, Nanchang 330006, People’sRepublic of China[4]Department of Pharmacy, Sun Yat-sen Memorial Hospital,SunYat-sen University, Guangzhou 510120, China中山大学附属第二医院[5]Guangdong Provincial Key Laboratory of Clinical Research onTraditional Chinese Medicine Syndrome, The Second AffiliatedHospital of Guangzhou University of Chinese Medicine,Guangzhou 510120, China[6]Department of Pharmacology & Toxicology, School ofPharmaceutical Sciences, Sun Yat-Sen University,Guangzhou 510080, China[7]International Joint Laboratory (SYSU-PolyU HK) of NovelAnti-Dementia Drugs of Guangdong, Guangzhou 510006, China[8]National and Local United Engineering Lab of Druggability and NewDrugs Evaluation, Sun Yat-Sen University, Guangzhou 510080,China
beta-amyloid protein (A beta) is thought to be the primary cause of the pathogenesis of Alzheimer's disease (AD). Niacin has been reported to have beneficial effects on AD. Previously, we synthesized a novel compound lipoicacid-niacin dimer (N2L) and revealed that it had potent blood-lipid regulation and antioxidative properties without aflushing effect. Given that lipid metabolism is also associated with AD, the present study aimed to investigate the neuroprotective effects of N2L on A beta(1-42)-induced cytotoxicity in HT22 cells. We found that N2L significantly attenuated cell apoptosis, MDA level, ROS content, and the mitochondrial membrane potential corruption induced by A beta(1-42) in HT22 cells. In addition, the activities of SOD, GSH-px and CAT that were decreased by A beta(1-42) were also restored by N2L. Furthermore, N2L reduced proapoptotic signaling by increasing the expression of anti-apoptotic Bcl-2 and decreasing the protein expression of both pro-apoptotic Bax and cleaved Caspase-3. Together, these findings indicate that N2L holds great potential for neuroprotection against A beta(1-42)-induced cytotoxicity via inhibition of oxidative stress and cell apoptosis, suggesting that N2L may be a promising agent for AD therapy.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81560662, 81803536]; Guangdong Provincial Key Laboratory of Construction Foundation [2017B030314030]; Science and Technology Planning Project of Guangdong Province [2016A020226036, 2016A020226011]; Shenzhen Basic Research Projects [JCYJ20170818100811018]; Health and Family Planning Commission of Jiangxi Province [20185520]
第一作者机构：[1]National Pharmaceutical Engineering Center for Solid Preparation inChinese Herbal Medicine, Jiangxi University of Traditional ChineseMedicine, Nanchang 330006, China[2]Guangdong Provincial Key Laboratory of New Drug Design andEvaluation, Shenzhen University Health Science Center,Shenzhen 518060, China
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Wang Rikang,Zhang Lang,Liao Rifang,et al.N2L, a novel lipoic acid-niacin dimer protects HT22 cells against beta-amyloid peptide-induced damage through attenuating apoptosis[J].METABOLIC BRAIN DISEASE.2019,34(6):1761-1770.doi:10.1007/s11011-019-00482-5.
APA：
Wang, Rikang,Zhang, Lang,Liao, Rifang,Li, Qian,Pi, Rongbiao&Yang, Xiaobo.(2019).N2L, a novel lipoic acid-niacin dimer protects HT22 cells against beta-amyloid peptide-induced damage through attenuating apoptosis.METABOLIC BRAIN DISEASE,34,(6)
MLA：
Wang, Rikang,et al."N2L, a novel lipoic acid-niacin dimer protects HT22 cells against beta-amyloid peptide-induced damage through attenuating apoptosis".METABOLIC BRAIN DISEASE 34..6(2019):1761-1770
