mTOR signaling: at the crossroads of plasticity, memory and disease.

mTOR signaling: at the crossroads of plasticity, memory and disease.
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DOI:
10.1016/j.tins.2009.11.003
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发表时间:
2010-02
影响因子:
15.9
通讯作者:
Klann, Eric
Klann, Eric
中科院分区:
医学1区
文献类型:
--
作者:
Hoeffer, Charles A.;Klann, Eric

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哺乳动物雷帕霉素靶蛋白(mTOR)是一种参与翻译控制和持久突触可塑性的蛋白激酶。mTOR作为两种多蛋白信号传导复合物mTORC 1和mTORC 2的中心组分发挥作用,这两种复合物可以基于其独特的组成和底物而彼此区分。虽然大多数将mTOR功能与突触可塑性联系起来的证据来自利用雷帕霉素的研究,但在转基因小鼠中的研究也表明,mTOR将受体与翻译机制偶联,以建立持久的突触变化,这是高级脑功能的基础,包括长期记忆。最后,mTOR信号级联的扰动似乎是人类神经系统疾病的常见病理生理学特征,包括精神发育迟滞综合征和自闭症谱系障碍。
Mammalian target of rapamycin (mTOR) is a protein kinase involved in translation control and long-lasting synaptic plasticity. mTOR functions as the central component of two multi-protein signaling complexes, mTORC1 and mTORC2, which can be distinguished from each other based on their unique compositions and substrates. Although majority of evidence linking mTOR function to synaptic plasticity comes from studies utilizing rapamycin, studies in genetically-modified mice also suggest that mTOR couples receptors to the translation machinery for establishing long-lasting synaptic changes that are the basis for higher order brain function, including long-term memory. Finally, perturbation of the mTOR signaling cascade appears to be a common pathophysiological feature of human neurological disorders, including mental retardation syndromes and autism spectrum disorders.
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