受伤引起的HDAC5核出口对于轴突再生至关重要
Yongcheol Cho1, Roman Sloutsky, Kristen M Naegle
1Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Cell
|November 12, 2013
概括
轴突损伤会触发波,导致HDAC5从核中输出. 这促进了外围神经元中轴突再生的基因表达,这是中枢神经系统损伤中缺失的途径.
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:
- 受伤后的轴突再生对于功能恢复至关重要.
- 重新激活静音转录程序是成功再生的关键.
- 将外围神经损伤与基因表达变化联系在一起的分子机制尚未完全理解.
研究的目的:
- 为了阐明在轴突受伤后解锁前再生基因表达的信号通路.
- 调查HDAC5在控制神经元生长能力受伤后的作用.
- 为了比较外周与中枢神经系统损伤中的再生反应.
主要方法:
- 在外围感官神经元中诱导轴突损伤.
- 监测波和HDAC5定位.
- 使用PKCμ抑制剂并表达突变的HDAC5.5.
- 评估轴突再生在体外和体内.
- 在中枢神经系统损伤模型中比较路径激活.
主要成果:
- 轴突损伤会产生波,导致PKCμ依赖的核出口HDAC5.5.
- 核出口HDAC5增强了基因素乙化,激活了亲再生基因表达.
- 阻止HDAC5核出口会抑制轴突再生,而促进它会增强再生.
- 在中枢神经系统损伤模型中,HDAC5通路组件没有被激活.
结论:
- 受伤引起的HDAC5核出口作为轴突再生的转录开关.
- 这种信号通路将损伤部位与神经元 soma 连接起来,控制生长潜力.
- 这些发现突显了外周神经系统和中枢神经系统之间再生能力的差异.
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