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Naturally occurring autoantibodies against A beta oligomers exhibited more beneficial effects in the treatment of mouse model of Alzheimer's disease than intravenous immunoglobulin
Wang, Teng1,2; Xie, Xi-xiu1; Ji, Mei1; Wang, Shao-wei1; Zha, Jun1; Zhou, Wei-wei1; Yu, Xiao-lin1; Wei, Chen4; Ma, Shan3; Xi, Zhi-ying3; Pang, Guang-li3; Liu, Rui-tian1
2016-06-01
发表期刊NEUROPHARMACOLOGY
ISSN0028-3908
卷号105期号:JUNE页码:561-576
摘要Alzheimer's disease (AD) is characterized by memory loss, intracellular neurofibrillary tangles, and extracellular plaque deposits composed of beta-amyloid (A beta). Previous reports showed that naturally occurring autoantibodies, such as intravenous immunoglobulin (IVIG), benefited patients with moderate-stage AD who carried an APOE-epsilon 4 allele. However, the mechanism underlying the role of IVIG remains unclear. In this study, we identified naturally occurring autoantibodies against A beta oligomers (NAbs-A beta o), which were purified by A beta 42 oligomer or Cibacron Blue affinity chromatography from IVIG and termed as Oli-NAbs and Blue-NAbs, respectively. Oli-NAbs and Blue-NAbs recognized A beta 42 oligomers or both A beta 40 and 42 oligomers, differently. Both antibodies inhibited A beta 42 aggregation and attenuated A beta 42-induced cytotoxicity. Compared with vehicles, Oli-NAbs, Blue-NAbs and IVIG significantly improved the memory and cognition, and reduced the soluble and oligomeric A beta levels in APPswe/PS1dE9 transgenic mice. Further investigation showed that Blue-NAbs at increased doses effectively decreased plaque burden and insoluble A beta levels, whereas Oli-NAbs significantly declined the microgliosis and astrogliosis, as well as the production of proinflammatory cytokines in vivo. Therefore, high levels of these antibodies against oligomeric A beta 40 or A beta 42 were required, correspondingly, to achieve the optimal effect. NAbs-A beta o could be condensed to a high concentration by affinity chromatography and its isolation from IVIG may not interfere with the normal function of conventional IVIG as its concentration is very low. Thus, the isolated NAbs-A beta o as an extra product of plasma required low cost and the enriched NAbs-A beta o may be more feasible than IVIG for the treatment of AD. (C) 2016 Elsevier Ltd. All rights reserved.
关键词Alzheimer's Disease Beta-amyloid Intravenous Immunoglobulin Oligomers Antibody
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine
DOI10.1016/j.neuropharm.2016.02.015
收录类别SCI
语种英语
关键词[WOS]AMYLOID-BETA ; MEMORY DEFICITS ; ANTIBODIES ; IMMUNOTHERAPY ; IMMUNIZATION ; PROTEIN ; MICROGLIA ; PEPTIDE ; TRIALS ; MICE
WOS研究方向Neurosciences & Neurology ; Pharmacology & Pharmacy
WOS类目Neurosciences ; Pharmacology & Pharmacy
项目资助者National Natural Science Foundation of China(81171014 ; National Science and Technology Major Projects of New Drugs(2012ZX09103301-001 ; 81371208) ; 2014ZX09102045-006 ; 2015ZX09102015)
WOS记录号WOS:000377311300053
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被引频次:8[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/20955
专题生化工程国家重点实验室
作者单位1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.AnHui Agr Univ, Sch Life Sci, Hefei 230036, Peoples R China
3.Shandong Inst Biol Prod, Tai An 2710000, Shandong, Peoples R China
4.Natl Inst Food & Drug Control, Beijing 100050, Peoples R China
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Wang, Teng,Xie, Xi-xiu,Ji, Mei,et al. Naturally occurring autoantibodies against A beta oligomers exhibited more beneficial effects in the treatment of mouse model of Alzheimer's disease than intravenous immunoglobulin[J]. NEUROPHARMACOLOGY,2016,105(JUNE):561-576.
APA Wang, Teng.,Xie, Xi-xiu.,Ji, Mei.,Wang, Shao-wei.,Zha, Jun.,...&Liu, Rui-tian.(2016).Naturally occurring autoantibodies against A beta oligomers exhibited more beneficial effects in the treatment of mouse model of Alzheimer's disease than intravenous immunoglobulin.NEUROPHARMACOLOGY,105(JUNE),561-576.
MLA Wang, Teng,et al."Naturally occurring autoantibodies against A beta oligomers exhibited more beneficial effects in the treatment of mouse model of Alzheimer's disease than intravenous immunoglobulin".NEUROPHARMACOLOGY 105.JUNE(2016):561-576.
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