GSK3 as a Sensor Determining Cell Fate in the Brain.
GSK3 as a Sensor Determining Cell Fate in the Brain.
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DOI：
10.3389/fnmol.2012.00004
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发表时间：
2012
影响因子：
4.8
通讯作者：
Cole AR
中科院分区：
文献类型：
--
作者：
Cole AR
糖原合成酶激酶3（GSK 3）是一种不常见的丝氨酸/苏氨酸激酶，其控制许多神经元功能，包括轴突生长、突触形成、神经传递和神经发生。它通过磷酸化参与基因转录、代谢、凋亡、细胞骨架动力学、信号转导、脂质膜动力学和运输等的广泛底物来介导这些功能。这种复杂的不同底物列表通常遵循更简单的模式：由GSK 3介导的磷酸化负调节的底物有利于增殖/存活状态，而由GSK 3正调节的底物有利于更分化/功能状态。因此，分化细胞中的GSK 3活性高于未分化细胞，并且GSK 3的生理学（Wnt，生长因子）和药理学抑制剂促进胚胎干细胞的增殖能力。在脑中，GSK 3活性水平影响神经可塑性和修复中的神经祖细胞增殖/分化，以及分化的成年神经元中的有效神经传递。虽然GSK 3活性的缺陷不太可能是神经退行性疾病的主要原因，但治疗性调节其活性以促进脑中的增殖/存活与分化/成熟功能环境可能是治疗神经退行性疾病和其他精神障碍的有力策略。
Glycogen synthase kinase 3 (GSK3) is an unusual serine/threonine kinase that controls many neuronal functions, including neurite outgrowth, synapse formation, neurotransmission, and neurogenesis. It mediates these functions by phosphorylating a wide range of substrates involved in gene transcription, metabolism, apoptosis, cytoskeletal dynamics, signal transduction, lipid membrane dynamics, and trafficking, amongst others. This complicated list of diverse substrates generally follow a more simple pattern: substrates negatively regulated by GSK3-mediated phosphorylation favor a proliferative/survival state, while substrates positively regulated by GSK3 favor a more differentiated/functional state. Accordingly, GSK3 activity is higher in differentiated cells than undifferentiated cells and physiological (Wnt, growth factors) and pharmacological inhibitors of GSK3 promote the proliferative capacity of embryonic stem cells. In the brain, the level of GSK3 activity influences neural progenitor cell proliferation/differentiation in neuroplasticity and repair, as well as efficient neurotransmission in differentiated adult neurons. While defects in GSK3 activity are unlikely to be the primary cause of neurodegenerative diseases, therapeutic regulation of its activity to promote a proliferative/survival versus differentiated/mature functional environment in the brain could be a powerful strategy for treatment of neurodegenerative and other mental disorders.
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影响因子：
5.3
作者：
Franco, B;Bogdanik, L;Grau, Y
通讯作者：
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影响因子：
11.8
作者：
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影响因子：
4.8
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作者：
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