Ao Chuncao, Li Chenchen, Chen Jinlun, Tan Jieqiong, Zeng Liuwang
Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, China.
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
Front Cell Neurosci. 2022 Jul 28;16:951202. doi: 10.3389/fncel.2022.951202. eCollection 2022.
Neurological disorders are a group of disorders with motor, sensory or cognitive damage, caused by dysfunction of the central or peripheral nervous system. Cyclin-dependent kinases 5 (Cdk5) is of vital significance for the development of the nervous system, including the migration and differentiation of neurons, the formation of synapses, and axon regeneration. However, when the nervous system is subject to pathological stimulation, aberrant activation of Cdk5 will induce abnormal phosphorylation of a variety of substrates, resulting in a cascade signaling pathway, and thus lead to pathological changes. Cdk5 is intimately related to the pathological mechanism of a variety of neurological disorders, such as A-β protein formation in Alzheimer's disease, mitochondrial fragmentation in cerebral ischemia, and apoptosis of dopaminergic neurons in Parkinson's disease. It is worth noting that Cdk5 inhibitors have been reported to have neuroprotective effects by inhibiting related pathological processes. Therefore, in this review, we will briefly introduce the physiological and pathological mechanisms of Cdk5 in the nervous system, focusing on the recent advances of Cdk5 in neurological disorders and the prospect of targeted Cdk5 for the treatment of neurological disorders.
神经疾病是由中枢或外周神经系统功能障碍引起的一组具有运动、感觉或认知损伤的疾病。细胞周期蛋白依赖性激酶5(Cdk5)对神经系统的发育至关重要,包括神经元的迁移和分化、突触的形成以及轴突再生。然而,当神经系统受到病理刺激时,Cdk5的异常激活会诱导多种底物的异常磷酸化,导致级联信号通路,进而引发病理变化。Cdk5与多种神经疾病的病理机制密切相关,如阿尔茨海默病中A-β蛋白的形成、脑缺血中线粒体的碎片化以及帕金森病中多巴胺能神经元的凋亡。值得注意的是,据报道Cdk5抑制剂可通过抑制相关病理过程发挥神经保护作用。因此,在本综述中,我们将简要介绍Cdk5在神经系统中的生理和病理机制,重点关注Cdk5在神经疾病中的最新进展以及靶向Cdk5治疗神经疾病的前景。