3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues A beta 42-Induced Loss of Human Neural Stem Cell Plasticity

doi:10.1016/j.devcel.2018.06.005

	3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues A beta 42-Induced Loss of Human Neural Stem Cell Plasticity
	Papadimitriou, Christos 1,2; Celikkaya, Hilal 1,2; Cosacak, Mehmet I.1,2; Mashkaryan, Violeta 1,2; Bray, Laura 3,4; Bhattarai, Prabesh 1,2; Brandt, Kerstin 1,2; Hollak, Heike 1,2; Chen, Xin5 ; He, Shuijin5 ; Antos, Christopher L.5,6 ; Lin, Weilin 7; Thomas, Alvin Kuriakose 7; Dahl, Andreas 2; Kurth, Thomas 2; Friedrichs, Jens 2,3; Zhang, Yixin 7; Freudenberg, Uwe 2,3; Werner, Carsten 2,3; Kizil, Caghan 1,2
	2018-07-02
发表期刊	DEVELOPMENTAL CELL (IF:10.7[JCR-2023],11.5[5-Year])
ISSN	1534-5807
卷号	46 期号:1 页码:85-+
发表状态	已发表
DOI	10.1016/j.devcel.2018.06.005
摘要	Neural stem cells (NSCs) constitute an endogenous reservoir for neurons that could potentially be harnessed for regenerative therapies in disease contexts such as neurodegeneration. However, in Alzheimer's disease (AD), NSCs lose plasticity and thus possible regenerative capacity. We investigate how NSCs lose their plasticity in AD by using starPEG-heparin-based hydrogels to establish a reductionist 3D cell-instructive neuro-microenvironment that promotes the proliferative and neurogenic ability of primary and induced human NSCs. We find that administration of AD-associated Amyloid-beta 42 causes classical neuropathology and hampers NSC plasticity by inducing kynurenic acid (KYNA) production. Interleukin-4 restores NSC proliferative and neurogenic ability by suppressing the KYNA-producing enzyme Kynurenine aminotransferase (KAT2), which is upregulated in APP/PS1dE9 mouse model of AD and in postmortem human AD brains. Thus, our culture system enables a reductionist investigation of regulation of human NSC plasticity for the identification of potential therapeutic targets for intervention in AD.
收录类别	SCI ; SCIE
语种	英语
资助项目	BMBF[PRECIMATRIX-FKZ-03XP0083-310117]
WOS研究方向	Cell Biology ; Developmental Biology
WOS类目	Cell Biology ; Developmental Biology
WOS记录号	WOS:000437232900009
出版者	CELL PRESS
WOS关键词	SUBVENTRICULAR ZONE ; AMYLOID-BETA ; HIPPOCAMPAL NEUROGENESIS ; BRAIN ; ASTROCYTES ; PROLIFERATION ; HYDROGELS ; PEPTIDE ; NEURODEGENERATION ; IDENTIFICATION
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/27418
专题	生命科学与技术学院生命科学与技术学院_PI研究组_Christopher Lee Antos组生命科学与技术学院_PI研究组_何水金组生命科学与技术学院_博士生
通讯作者	Kizil, Caghan
作者单位	1.Helmholtz Assoc, German Ctr Neurodegenerat Dis DZNE Dresden, Arnoldstr 18, D-01307 Dresden, Germany 2.Tech Univ Dresden, Ctr Regenerat Therapies CRTD, Fetscherstr 105, D-01307 Dresden, Germany 3.Max Bergmann Ctr Biomat Dresden, Leibniz Inst Polymer Res Dresden, Hohe Str 6, D-01069 Dresden, Germany 4.Queensland Univ Technol, Inst Hlth Biomed Innovat, 60 Musk Ave, Kelvin Grove 4059, Australia 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.Tech Univ Dresden, Inst Pharmakol & Toxikol, Med Fak, Fetscherstr 74, D-01307 Dresden, Germany 7.Tech Univ Dresden, Ctr Mol Bioengn, B CUBE, Arnoldstr 18, D-10307 Dresden, Germany
推荐引用方式 GB/T 7714	Papadimitriou, Christos,Celikkaya, Hilal,Cosacak, Mehmet I.,et al. 3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues A beta 42-Induced Loss of Human Neural Stem Cell Plasticity[J]. DEVELOPMENTAL CELL,2018,46(1):85-+.
APA	Papadimitriou, Christos.,Celikkaya, Hilal.,Cosacak, Mehmet I..,Mashkaryan, Violeta.,Bray, Laura.,...&Kizil, Caghan.(2018).3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues A beta 42-Induced Loss of Human Neural Stem Cell Plasticity.DEVELOPMENTAL CELL,46(1),85-+.
MLA	Papadimitriou, Christos,et al."3D Culture Method for Alzheimer's Disease Modeling Reveals Interleukin-4 Rescues A beta 42-Induced Loss of Human Neural Stem Cell Plasticity".DEVELOPMENTAL CELL 46.1(2018):85-+.