Howard Hughes Medical Institute, Cambridge, Massachusetts 02139, USA.
Annu Rev Cell Dev Biol. 2011;27:465-91. doi: 10.1146/annurev-cellbio-092910-154023. Epub 2011 Jul 5.
Cyclin-dependent kinase 5 (Cdk5) is a multifaceted serine/threonine kinase protein with important roles in the nervous system. Two related proteins, p35 and p39, activate Cdk5 upon direct binding. Over the past decade, Cdk5 activity has been demonstrated to regulate many events during brain development, including neuronal migration as well as axon and dendrite development. Recent evidence also suggests a pivotal role for Cdk5 in synaptic plasticity, behavior, and cognition. Dysfunction of Cdk5 has been implicated in a number of neurological disorders and neurodegenerative diseases including Alzheimer's disease, amyotrophic lateral sclerosis, Niemann-Pick type C disease, and ischemia. Hyperactivation of Cdk5 due to the conversion of p35 to p25 by the calcium-dependent protease calpain during neurotoxicity also contributes to the pathological state. This review surveys recent literature surrounding Cdk5 in synaptic plasticity and homeostasis, with particular emphasis on Cdk5 kinase activity under neurodegenerative conditions.
周期蛋白依赖性激酶 5（Cdk5）是一种多功能丝氨酸/苏氨酸激酶蛋白，在神经系统中具有重要作用。两种相关蛋白，p35 和 p39，通过直接结合激活 Cdk5。在过去的十年中，Cdk5 的活性已被证明可调节大脑发育过程中的许多事件，包括神经元迁移以及轴突和树突的发育。最近的证据还表明 Cdk5 在突触可塑性、行为和认知中起着关键作用。Cdk5 的功能障碍与许多神经退行性疾病有关，包括阿尔茨海默病、肌萎缩侧索硬化症、尼曼-皮克 C 型疾病和缺血性疾病。钙依赖性蛋白酶钙蛋白酶在神经毒性过程中将 p35 转化为 p25 会导致 Cdk5 的过度激活，这也导致了病理状态。本综述调查了围绕突触可塑性和动态平衡的 Cdk5 的最新文献，特别强调了神经退行性条件下 Cdk5 激酶活性。
