A Novel 2-Phenylamino-Quinazoline-Based Compound Expands the Neural Stem Cell Pool and Promotes the Hippocampal Neurogenesis and the Cognitive Ability of Adult Mice

doi:10.1002/stem.2843

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药理学第二研究室

	A Novel 2-Phenylamino-Quinazoline-Based Compound Expands the Neural Stem Cell Pool and Promotes the Hippocampal Neurogenesis and the Cognitive Ability of Adult Mice
	Lu, Hui 2,3; Cheng, Gang 1,4; Hong, Feng 2,3; Zhang, Lei 2,3; Hu, Youhong1,3 ; Feng, Linyin2,3
刊名	STEM CELLS
	2018-08
卷号	36 期号:8 页码:1273-1285
关键词	Neural stem cells Notch signaling pathway Hes5 Adult hippocampal neurogenesis Learning and memory 2-phenylamino-quinazoline
ISSN号	1066-5099
DOI	10.1002/stem.2843
文献子类	Article
英文摘要	The adult neurogenesis occurs throughout the life of the mammalian hippocampus and is found to be essential for learning and memory. Identifying new ways to manipulate the number of neural stem cells (NSCs) and enhance endogenous neurogenesis in adults is very important. Here we found that a novel compound, N2-(4-isopropylphenyl)-5-(3-methoxyphenoxy)quinazoline-2,4-diamine (code-named Yhhu-3792), enhanced the self-renewal capability of NSCs in vitro and in vivo. In vitro, Yhhu-3792 increased the ratio of 5-Bromo-2-deoxyuridine(+)/4'-6-diamidino-2-phenylindole(+) embryonic NSCs and accelerated the growth of neurospheres significantly. We demonstrated that Yhhu-3792 activated Notch signaling pathway and promoted the expression of Notch target genes, Hes3 and Hes5. And the Notch signaling inhibitor DAPT could inhibit its function. Thus, we concluded Yhhu-3792 increased the number of embryonic NSCs via activating the Notch signaling pathway. We measured the effect of Yhhu-3792 on epidermal growth factor receptor signaling, which demonstrated Yhhu-3792 act via a different mechanism with the quinazoline parent chemical group. In the eight-week-old male C57BL/6 mice, chronic Yhhu-3792 administration expanded the NSCs pool and promoted endogenous neurogenesis in the hippocampal dentate gyrus (DG). It also increased the spatial and episodic memory abilities of mice, when evaluated with the Morris water maze and Fear conditioning tests. In conclusion, Yhhu-3792 could be a novel drug candidate to promote the self-renew of NSCs and adult neurogenesis. And it may have therapeutic potential in the impairment of learning and memory associated DG dysfunction.
资助项目	"Key New Drug Creation and Manufacturing Program" of the National Science and Technology Major Project[2014ZX09102-001-05] ; Scientific Innovation Project of the Chinese Academy of Sciences[XDA 01040304]
WOS关键词	FIBROBLAST-GROWTH-FACTOR ; DENTATE GYRUS ; SELF-RENEWAL ; NOTCH ; MEMORY ; PROLIFERATION ; BRAIN ; PROTEIN ; CANCER ; DRUGS
WOS研究方向	Cell Biology ; Biotechnology & Applied Microbiology ; Oncology ; Hematology
语种	英语
出版者	WILEY
WOS记录号	WOS:000441443900014
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279644]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Feng, Linyin
作者单位	1.Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 2.Univ Chinese Acad Sci, Shanghai Inst Mat Med, Dept Neuropharmacol, CAS Key Lab Receptor Res, Shanghai, Peoples R China; 3.Univ Chinese Acad Sci, Beijing, Peoples R China; 4.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou, Zhejiang, Peoples R China;
推荐引用方式 GB/T 7714	Lu, Hui,Cheng, Gang,Hong, Feng,et al. A Novel 2-Phenylamino-Quinazoline-Based Compound Expands the Neural Stem Cell Pool and Promotes the Hippocampal Neurogenesis and the Cognitive Ability of Adult Mice[J]. STEM CELLS,2018,36(8):1273-1285.
APA	Lu, Hui,Cheng, Gang,Hong, Feng,Zhang, Lei,Hu, Youhong,&Feng, Linyin.(2018).A Novel 2-Phenylamino-Quinazoline-Based Compound Expands the Neural Stem Cell Pool and Promotes the Hippocampal Neurogenesis and the Cognitive Ability of Adult Mice.STEM CELLS,36(8),1273-1285.
MLA	Lu, Hui,et al."A Novel 2-Phenylamino-Quinazoline-Based Compound Expands the Neural Stem Cell Pool and Promotes the Hippocampal Neurogenesis and the Cognitive Ability of Adult Mice".STEM CELLS 36.8(2018):1273-1285.