激活mTOR途径通过对CD44表达的上调促进神经元生长
Jiwei Zhang1, Wenjuan Gan1, Ru Peng2
1Department of Pathology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, 215123, China.
The Journal of international medical research
|June 21, 2023
概括
激活哺乳动物目标的拉巴胺素 (mTOR) 途径通过调节分化44 (CD44) 表达的集群,增强神经元生长,促进神经元再生.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 神经元再生对于从神经损伤中恢复至关重要.
- 哺乳动物的目标拉巴素 (mTOR) 途径在细胞生长和存活中起作用.
- 了解神经元轴突生长的机制对于开发治疗策略至关重要.
研究的目的:
- 阐明了哺乳动物目标拉巴素 (mTOR) 途径被激活的内在机制.
- 研究mTOR通路激活在促进神经元轴突生长中的作用.
- 探索酸酶和张素同类素 (PTEN),分化44 (CD44) 集群和神经元再生之间的关系.
主要方法:
- 人类神经母细胞SH-SY5Y细胞通过全转网红酸 (ATRA) 分化成神经元样状态.
- 用RNA干扰 (RNAi) 降低酸酶和张素同源 (PTEN) 和分化44集群 (CD44) 的下调.
- 基因和蛋白质表达水平的PTEN,mTOR,pS6k和CD44使用RT-PCR和西部斑点测试进行了分析. 测量神经元长度以评估轴突生长.
主要成果:
- 降低PTEN的调节导致mTOR和ps6k蛋白表达的显著上调.
- PTEN干扰也导致CD44转录水平的增加.
- 低调PTEN的细胞表现出明显更长的神经元,CD44表达与神经元生长有积极的相关性.
结论:
- 激活mTOR通路促进神经元外生和神经元再生.
- CD44表达的升级是mTOR途径增强轴突生长的关键机制.
- 针对mTOR-CD44轴是一个潜在的治疗策略,可以促进神经元的修复.
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