灵芝多糖对阿尔茨海默病小鼠模型认知功能及神经祖细胞增殖的促进作用

Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer's Disease.

作者信息

Huang Shichao, Mao Jianxin, Ding Kan, Zhou Yue, Zeng Xianglu, Yang Wenjuan, Wang Peipei, Zhao Cun, Yao Jian, Xia Peng, Pei Gang

机构信息

Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.

State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China; Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, China.

出版信息

Stem Cell Reports. 2017 Jan 10;8(1):84-94. doi: 10.1016/j.stemcr.2016.12.007.

Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimer's disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G. lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G. lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture. Further mechanistic study revealed that GLP potentiated activation of fibroblast growth factor receptor 1 (FGFR1) and downstream extracellular signal-regulated kinase (ERK) and AKT cascades. Consistently, inhibition of FGFR1 effectively blocked the GLP-promoted NPC proliferation and activation of the downstream cascades. Our findings suggest that GLP could serve as a regenerative therapeutic agent for the treatment of cognitive decline associated with neurodegenerative diseases.

促进神经发生是治疗与阿尔茨海默病（AD）相关的认知障碍的一种有前景的策略。灵芝是一种在东方备受推崇的具有促进健康功效的药用蘑菇。在此，我们发现口服灵芝多糖和水提取物可促进神经祖细胞（NPC）增殖以增强神经发生，并减轻转基因AD小鼠的认知缺陷。灵芝多糖（GLP）在细胞培养中也促进了NPC的自我更新。进一步的机制研究表明，GLP增强了成纤维细胞生长因子受体1（FGFR1）以及下游细胞外信号调节激酶（ERK）和AKT级联反应的激活。同样，抑制FGFR1可有效阻断GLP促进的NPC增殖和下游级联反应的激活。我们的研究结果表明，GLP可作为一种再生治疗剂用于治疗与神经退行性疾病相关的认知衰退。