Department of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong, 250012, People's Republic of China.
Mol Neurobiol. 2024 Oct;61(10):7287-7302. doi: 10.1007/s12035-024-04047-1. Epub 2024 Feb 20.
Neurodegenerative diseases are a group of diseases characterized by the progressive loss of neurons, including Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis. These diseases have a high incidence and mortality rate globally, placing a heavy burden on patients and their families. The pathogenesis of neurodegenerative diseases is complex, and there are no effective treatments at present. Cyclin-dependent kinase 5 is a proline-directed serine/threonine protein kinase that is closely related to the development and function of the nervous system. Under physiological conditions, it is involved in regulating the process of neuronal proliferation, differentiation, migration, and synaptic plasticity. Moreover, there is increasing evidence that cyclin-dependent kinase 5 also plays an important role in the pathogenesis of neurodegenerative diseases. In this review, we address the biological characteristics of cyclin-dependent kinase 5 and its role in neurodegenerative diseases. In particular, this review highlights the underlying mechanistic linkages between cyclin-dependent kinase 5 and mitochondrial dysfunction, oxidative stress and neuroinflammation in the context of neurodegeneration. Finally, we also summarize the currently available cyclin-dependent kinase 5 inhibitors and their prospects for the treatment of neurodegenerative diseases. Taken together, a better understanding of the molecular mechanisms of cyclin-dependent kinase 5 involved in neurodegenerative diseases can lead to the development of new strategies for the prevention and treatment of these devastating diseases.
神经退行性疾病是一组以神经元进行性丧失为特征的疾病，包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。这些疾病在全球范围内发病率和死亡率都很高，给患者及其家庭带来了沉重的负担。神经退行性疾病的发病机制复杂，目前尚无有效的治疗方法。细胞周期蛋白依赖性激酶 5 是一种脯氨酸导向的丝氨酸/苏氨酸蛋白激酶，与神经系统的发育和功能密切相关。在生理条件下，它参与调节神经元增殖、分化、迁移和突触可塑性的过程。此外，越来越多的证据表明，细胞周期蛋白依赖性激酶 5 也在神经退行性疾病的发病机制中发挥重要作用。在这篇综述中，我们探讨了细胞周期蛋白依赖性激酶 5 的生物学特性及其在神经退行性疾病中的作用。特别是，本综述强调了细胞周期蛋白依赖性激酶 5 与线粒体功能障碍、氧化应激和神经炎症在神经退行性变中的潜在机制联系。最后，我们还总结了目前可用的细胞周期蛋白依赖性激酶 5 抑制剂及其在治疗神经退行性疾病方面的前景。总之，更好地理解细胞周期蛋白依赖性激酶 5 参与神经退行性疾病的分子机制，可以为预防和治疗这些毁灭性疾病提供新的策略。
