Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
J Biomed Sci. 2021 Nov 23;28(1):79. doi: 10.1186/s12929-021-00774-y.
Cdk5 is a proline-directed serine/threonine protein kinase that governs a variety of cellular processes in neurons, the dysregulation of which compromises normal brain function. The mechanisms underlying the modulation of Cdk5, its modes of action, and its effects on the nervous system have been a great focus in the field for nearly three decades. In this review, we provide an overview of the discovery and regulation of Cdk5, highlighting recent findings revealing its role in neuronal/synaptic functions, circadian clocks, DNA damage, cell cycle reentry, mitochondrial dysfunction, as well as its non-neuronal functions under physiological and pathological conditions. Moreover, we discuss evidence underscoring aberrant Cdk5 activity as a common theme observed in many neurodegenerative diseases.
Cdk5 是一种脯氨酸导向的丝氨酸/苏氨酸蛋白激酶，它调控神经元中的多种细胞过程，其失调会损害正常的大脑功能。近三十年来，Cdk5 的调节机制、作用方式及其对神经系统的影响一直是该领域的研究重点。在这篇综述中，我们概述了 Cdk5 的发现和调节，强调了最近的发现揭示了它在神经元/突触功能、生物钟、DNA 损伤、细胞周期再进入、线粒体功能以及生理和病理条件下的非神经元功能中的作用。此外，我们还讨论了异常的 Cdk5 活性作为许多神经退行性疾病中观察到的共同主题的证据。
