机构：[1]Department of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, China,[2]Department of Neurosurgery, Guangzhou Women and Children’s Medical Center, Guangzhou, China,[3]Institute of Brain Sciences, Jinan University, Guangzhou, China,[4]Department of Neurosurgery, The First Affiliated Hospital of Jinan University, Guangzhou, China,[5]Guangzhou Quality R&D Center of Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-sen University, Guangzhou, China
Neural stem cells (NSCs) have been shown as a potential source for replacing degenerated neurons in neurodegenerative diseases. However, the therapeutic potential of these cells is limited by the lack of effective methodologies for controlling their differentiation. Inducing endogenous pools of NSCs by small molecule can be considered as a potential approach of generating the desired cell types in large numbers. Here, we reported the characterization of a small molecule (Methyl 3,4-dihydroxybenzoate; MDHB) that selectively induces hippocampal NSCs to differentiate into cholinergic motor neurons which expressed synapsin 1 (SYN1) and postsynaptic density protein 95 (PSD-95). Studies on the mechanisms revealed that MDHB induced the hippocampal NSCs differentiation into cholinergic motor neurons by inhibiting AKT phosphorylation and activating autophosphorylation of GSK3β at tyrosine 216. Furthermore, we found that MDHB enhanced β-catenin degradation and abolished its entering into the nucleus. Collectively, this report provides the strong evidence that MDHB promotes NSCs differentiation into cholinergic motor neurons by enhancing gene Isl1 expression and inhibiting cell cycle progression. It may provide a basis for pharmacological effects of MDHB directed on NSCs.
基金：
This research was funded by grants from the National
Natural Science Foundation of China (No. 81473296), and the
Guangdong Provincial Department of Science and Technology,
China (No. 2012B050300018).
第一作者机构：[1]Department of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, China,[2]Department of Neurosurgery, Guangzhou Women and Children’s Medical Center, Guangzhou, China,
共同第一作者：
通讯作者：
通讯机构：[1]Department of Pharmacology, College of Basic Medicine, Jinan University, Guangzhou, China,[3]Institute of Brain Sciences, Jinan University, Guangzhou, China,
推荐引用方式(GB/T 7714)：
Jun-Ping Pan,Yang Hu,Jia-Hui Wang,et al.Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro.[J].FRONTIERS IN CELLULAR NEUROSCIENCE.2018,12:doi:10.3389/fncel.2018.00478.
APA：
Jun-Ping Pan,Yang Hu,Jia-Hui Wang,Yi-Rong Xin,Jun-Xing Jiang...&Huan-Min Luo.(2018).Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro..FRONTIERS IN CELLULAR NEUROSCIENCE,12,
MLA：
Jun-Ping Pan,et al."Methyl 3,4-Dihydroxybenzoate Induces Neural Stem Cells to Differentiate Into Cholinergic Neurons in vitro.".FRONTIERS IN CELLULAR NEUROSCIENCE 12.(2018)
