Theoretical and Applied Sciences, Division of Biomedical Research, University of Insubria, 21052 Busto Arsizio, Italy.
Neural Plast. 2012;2012:728267. doi: 10.1155/2012/728267. Epub 2012 Jun 17.
In the last few years, the X-linked serine/threonine kinase cyclin-dependent kinase-like 5 (CDKL5) has been associated with early-onset epileptic encephalopathies characterized by the manifestation of intractable epilepsy within the first weeks of life, severe developmental delay, profound hypotonia, and often the presence of some Rett-syndrome-like features. The association of CDKL5 with neurodevelopmental disorders and its high expression levels in the maturing brain underscore the importance of this kinase for proper brain development. However, our present knowledge of CDKL5 functions is still rather limited. The picture that emerges from the molecular and cellular studies suggests that CDKL5 functions are important for regulating both neuronal morphology through cytoplasmic signaling pathways and activity-dependent gene expression in the nuclear compartment. This paper surveys the current state of CDKL5 research with emphasis on the clinical symptoms associated with mutations in CDKL5, the different mechanisms regulating its functions, and the connected molecular pathways. Finally, based on the available data we speculate that CDKL5 might play a role in neuronal plasticity and we adduce and discuss some possible arguments supporting this hypothesis.
在过去的几年中，X 连锁丝氨酸/苏氨酸激酶细胞周期蛋白依赖性激酶样 5（CDKL5）与早发性癫痫性脑病有关，其特征是在生命的头几周内表现出难治性癫痫、严重的发育迟缓、明显的肌张力低下，并且常常存在一些雷特综合征样特征。CDKL5 与神经发育障碍的关联及其在成熟大脑中的高表达水平强调了这种激酶对正常大脑发育的重要性。然而，我们目前对 CDKL5 功能的了解仍然相当有限。分子和细胞研究呈现的图景表明，CDKL5 功能对于通过细胞质信号通路调节神经元形态以及核区活性依赖性基因表达非常重要。本文综述了 CDKL5 研究的现状，重点介绍了与 CDKL5 突变相关的临床症状、调节其功能的不同机制以及相关的分子途径。最后，根据现有数据，我们推测 CDKL5 可能在神经元可塑性中发挥作用，并提出并讨论了一些支持这一假设的可能论据。
