Functional inhibition of the p75 receptor using a small interfering RNA

Functional inhibition of the p75 receptor using a small interfering RNA
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DOI:
10.1016/s0006-291x(03)00029-9
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发表时间:
2003-02-14
影响因子:
3.1
通讯作者:
Tohyama, M
Tohyama, M
中科院分区:
生物学4区
文献类型:
--
作者:
Higuchi, H;Yamashita, T;Tohyama, M

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神经营养因子受体p75(NTR)介导多种生物学效应。与控制存活和神经突形成的功能一致,p75(NTR)在神经系统的发育阶段表达。重要的是,p75(NTR)在各种病理条件下重新表达,并被认为有助于抑制神经元再生和神经元死亡。在这里,我们开发了一种工具,敲低p75(NTR)的表达,通过采用小干扰RNA(siRNA)。针对p75(NTR)的siRNA在体外有效地降低雪旺细胞和背根神经节神经元中内源性p75(NTR)的表达。NGF诱导的雪旺细胞中的细胞死亡和髓鞘相关糖蛋白诱导的DRG神经元中的轴突回缩被siRNA减弱。通过siRNA在特定病理条件下抑制p75(NTR)可以提供潜在的治疗剂。(C)2003 Elsevier Science(美国)。All rights reserved.
The neurotrophin receptor p75(NTR) mediates a wide variety of biological effects. Consistent with the function in controlling the survival and neurite formation, p75(NTR) is expressed during the developmental stages of the nervous system. Importantly, p75(NTR) is re-expressed in various pathological conditions and is suggested to contribute to the inhibition of neuronal regeneration and the death of the neurons. Here we develop a tool to knock down the expression of p75(NTR) by employing a small interfering RNA (siRNA). The siRNA for p75(NTR) effectively reduces the expression of endogenous p75(NTR) both in Schwann cells and dorsal root ganglion neurons in vitro. NGF-induced cell death in Schwann cells and the neurite retraction in DRG neurons induced by myelin-associated glycoprotein are attenuated by the siRNA. Inhibition of p75(NTR) in specific pathological conditions by the siRNA may provide a potential therapeutic agent. (C) 2003 Elsevier Science (USA). All rights reserved.