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Regulators of the G1 Phase of the Cell Cycle and Neurogenesis

机译:细胞周期和神经发生的G1期调节因子

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During neurogenesis, precursor cells undergo a defined number of divisions and terminally differentiate as postmitotic neurons. In the adult mammal, under certain conditions, postmitotic neurons re-enter the cell cycle and divide. The accumulated evidence demonstrates that the precise control of cell-cycle progression is critical for both neuronal development and maintenance of the neuronal phenotype. Cyclin-dependent Kinase Inhibitors (CDKIs) play the key role in this neuronal differentiation process of coordinating cell cycle exit and differentiation. Importantly, deregulation of the cell cycle leads to a variety of human neuronal diseases. In this review we discuss how regulation of neuronal progenitor proliferation and neuronal differentiation are coupled processes, based on evidence derived from the study of multiple animal models (mouse, Drosophila and Xenopus). In addition, we discuss the involvement of CDKIs in human neuronal diseases including cancers of neuronal systems, Alzheimer ’ s disease, and psychological disorders, and their potential as pharmacological targets.
机译:在神经发生过程中,前体细胞经历一定数量的分裂,并最终分化为有丝分裂后神经元。在成年哺乳动物中,在某些条件下,有丝分裂后神经元重新进入细胞周期并分裂。累积的证据表明,细胞周期进程的精确控制对于神经元发育和神经元表型的维持至关重要。细胞周期蛋白依赖性激酶抑制剂(CDKI)在协调细胞周期退出和分化的神经元分化过程中起关键作用。重要的是,细胞周期的失调导致多种人类神经元疾病。在这篇综述中,我们基于对多种动物模型(小鼠,果蝇和非洲爪蟾)的研究得出的证据,讨论神经元祖细胞增殖的调节和神经元分化的调控是如何耦合的。此外,我们讨论了CDKI与人类神经元疾病(包括神经元系统癌症,阿尔茨海默氏病和心理疾病)的关系,以及它们作为药理学靶标的潜力。

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