Instituto de Neurociencias, CSIC and Universidad Miguel Hernandez, Alicante, Spain.
FEBS J. 2011 Jan;278(2):223-35. doi: 10.1111/j.1742-4658.2010.07954.x. Epub 2010 Dec 13.
MNB/DYRK1A is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family that has been strongly conserved across evolution. There are substantial data implicating MNB/DYRK1A in brain development and adult brain function, as well as in neurodegeneration and Down syndrome pathologies. Here we review our current understanding of the neurodevelopmental activity of MNB/DYRK1A. We discuss how MNB/DYRK1A fulfils several sequential roles in neuronal development and the molecular mechanisms possibly underlying these functions. We also summarize the evidence behind the hypotheses to explain how the imbalance in MNB/DYRK1A gene dosage might be implicated in the neurodevelopmental alterations associated with Down syndrome. Finally, we highlight some research directions that may help to clarify the mechanisms and functions of MNB/DYRK1A signalling in the developing brain.
MNB/DYRK1A 是双特异性酪氨酸磷酸化调节激酶 (DYRK) 家族的成员,在进化过程中得到了很好的保守。有大量数据表明 MNB/DYRK1A 与脑发育和成年脑功能以及神经退行性变和唐氏综合征病理有关。在这里,我们回顾了我们对 MNB/DYRK1A 的神经发育活性的现有认识。我们讨论了 MNB/DYRK1A 如何在神经元发育中发挥几个连续的作用,以及这些功能可能的分子机制。我们还总结了支持这些假说的证据,以解释 MNB/DYRK1A 基因剂量失衡如何与唐氏综合征相关的神经发育改变有关。最后,我们强调了一些研究方向,这些方向可能有助于阐明 MNB/DYRK1A 信号在发育中的大脑中的机制和功能。