PTEN deletion enhances the regenerative ability of adult corticospinal neurons.
PTEN deletion enhances the regenerative ability of adult corticospinal neurons.
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DOI：
10.1038/nn.2603
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发表时间：
2010-09
影响因子：
25
通讯作者：
He, Zhigang
中科院分区：
文献类型：
--
作者：
Liu, Kai;Lu, Yi;Lee, Jae K.;Samara, Ramsey;Willenberg, Rafer;Sears-Kraxberger, Ilse;Tedeschi, Andrea;Park, Kevin Kyungsuk;Jin, Duo;Cai, Bin;Xu, Bengang;Connolly, Lauren;Steward, Oswald;Zheng, Binhai;He, Zhigang
尽管皮质脊髓束（CST）在控制随意运动中起着重要作用，但从未实现过脊髓损伤后大量受损CST轴突的成功再生。在这里，我们证明了一个关键的参与PTEN/mTOR在控制小鼠皮质脊髓神经元的再生能力。发育完成后，CST轴突的再生潜力丧失，这伴随着皮质脊髓神经元中mTOR活性的下调。轴突损伤进一步减少这些神经元中的神经元mTOR活性。通过条件性缺失PTEN（mTOR的负调节因子）强制上调皮质脊髓神经元中的mTOR活性，增强了未受伤的CST轴突的补偿性发芽，并且甚至更引人注目的是，能够使一组受伤的CST轴突通过脊髓病变成功再生。此外，这些再生的CST轴突具有在损伤远端的脊髓节段中改革突触的能力。因此，调节神经元内源性PTEN/mTOR活性代表了促进成年脊髓损伤后轴突再生和功能修复的潜在治疗策略。
Despite the essential role of the corticospinal tract (CST) in controlling voluntary movements, successful regeneration of large numbers of injured CST axons beyond a spinal cord lesion has never been achieved. Here we demonstrate a critical involvement of PTEN/mTOR in controlling the regenerative capacity of mouse corticospinal neurons. Upon the completion of development, the regrowth potential of CST axons lost and this is accompanied by a down-regulation of mTOR activity in corticospinal neurons. Axonal injury further diminishes neuronal mTOR activity in these neurons. Forced up-regulation of mTOR activity in corticospinal neurons by conditional deletion of PTEN, a negative regulator of mTOR, enhances compensatory sprouting of uninjured CST axons and even more strikingly, enables successful regeneration of a cohort of injured CST axons past a spinal cord lesion. Furthermore, these regenerating CST axons possess the ability to reform synapses in spinal segments distal to the injury. Thus, modulating neuronal intrinsic PTEN/mTOR activity represents a potential therapeutic strategy for promoting axon regeneration and functional repair after adult spinal cord injury.
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影响因子：
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