Hämmerle B, Elizalde C, Galceran J, Becker W, Tejedor F J
Instituto de Neurociencias, Unidad de Neurobiologia del Desarrollo, CSIC y Universidad Miguel Hernandez, Campus de San Juan, San Juan (Alicante), Spain.
J Neural Transm Suppl. 2003(67):129-37. doi: 10.1007/978-3-7091-6721-2_11.
Major attention is being paid in recent years to the genes harbored within the so called Down syndrome Critical Region of human chromosome 21. Among them, those genes with a possible brain function are becoming the focus of intense research due to the numerous neurobiological alterations and cognitive deficits that Down syndrome individuals have. MNB/DYRK1A is one of these genes. It encodes a protein kinase with unique genetic and biochemical properties, which have been evolutionarily conserved from insects to humans. MNB/DYRK1A is expressed in the developing brain where it seems to play a role in proliferation of neural progenitor cells, neurogenesis, and neuronal differentiation. Although at a lower level, MNB/DYRK1A is also expressed in the adult brain where, as judged by the phenotype of mutant and transgenic animals, it may be involved in learning and memory. Nevertheless, most of the molecular mechanisms underlying these functions remain to be unraveled. In this review we compile and discuss experimental evidences, which support the involvement of MNB/DYRK1A in several neuropathologies and cognitive deficits of Down syndrome.
近年来，人们主要关注人类21号染色体上所谓的唐氏综合征关键区域内的基因。其中，那些可能具有脑功能的基因正成为深入研究的焦点，这是因为唐氏综合征患者存在众多神经生物学改变和认知缺陷。MNB/DYRK1A就是这些基因之一。它编码一种具有独特遗传和生化特性的蛋白激酶，这种特性从昆虫到人类在进化过程中一直保守。MNB/DYRK1A在发育中的大脑中表达，似乎在神经祖细胞增殖、神经发生和神经元分化中发挥作用。尽管表达水平较低，但MNB/DYRK1A在成人大脑中也有表达，从突变和转基因动物的表型判断，它可能参与学习和记忆。然而，这些功能背后的大多数分子机制仍有待阐明。在这篇综述中，我们汇编并讨论了支持MNB/DYRK1A参与唐氏综合征的几种神经病理学和认知缺陷的实验证据。
