Laboratory of Neurosciences, Faculty of Sciences, University of Chile, Santiago, Chile.
International Center for Biomedicine (ICC), Santiago, Chile.
J Alzheimers Dis. 2019;68(3):843-855. doi: 10.3233/JAD-180792.
The cyclin-dependent kinase 5 (CDK5) is known as an exceptional component of the CDK family, due to its characteristic regulatory pathways and its atypical roles in comparison to the classical cyclins. Despite its functional uniqueness, CDK5 shares a great part of its structural similarity with other members of the cyclin-dependent kinase family. After its discovery 26 years ago, a progressive set of cellular functions has been associated with this protein kinase, ranging from neuronal migration, axonal guidance, and synaptic plasticity in diverse stages of brain development, including specific and complex cognitive functions. More than 30 substrates for CDK5 have been found in different cellular pathways. Together with its essential physiological roles, a major discovery was the finding twenty years ago that CDK5 participates in neurodegenerative diseases responsible for tau hyperphosphorylations, and, as a consequence, it becomes a neurotoxic factor. This review focuses on the wide roles of CDK5 in the central nervous system, its implications in neurodegeneration, and provides an integrative insight of its involvement in pain modulation, Alzheimer's disease, and other contexts.
周期蛋白依赖性激酶 5（CDK5）是 CDK 家族中的一个特殊组成部分，因其调节途径的特征和与经典周期蛋白相比的非典型作用而得名。尽管 CDK5 的功能独特，但它与细胞周期蛋白依赖性激酶家族的其他成员在结构上有很大的相似性。在 26 年前发现它之后，人们逐渐发现了这种蛋白激酶在大脑发育的不同阶段的多种细胞功能，包括特定和复杂的认知功能，如神经元迁移、轴突导向和突触可塑性。在不同的细胞途径中已经发现了超过 30 种 CDK5 的底物。除了其重要的生理作用外，二十年前的一项重大发现是 CDK5 参与了导致 tau 过度磷酸化的神经退行性疾病，因此它成为一种神经毒性因子。本文综述了 CDK5 在中枢神经系统中的广泛作用、在神经退行性变中的意义，并对其在疼痛调节、阿尔茨海默病及其他方面的作用提供了综合的见解。
