Zhu Kedong, Wang Hualong, Ye Keqiang, Chen Guiqin, Zhang Zhaohui
Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.
Department of Neurology, The First Hospital of Hebei Medical University; Brain Aging and Cognitive Neuroscience Laboratory of Heibei Province, Shijiazhuang, Hebei Province, China.
Neural Regen Res. 2025 Apr 1;20(4):960-972. doi: 10.4103/NRR.NRR-D-23-01573. Epub 2024 May 13.
Netrin-1 and its receptors play crucial roles in inducing axonal growth and neuronal migration during neuronal development. Their profound impacts then extend into adulthood to encompass the maintenance of neuronal survival and synaptic function. Increasing amounts of evidence highlight several key points: (1) Diminished Netrin-1 levels exacerbate pathological progression in animal models of Alzheimer's disease and Parkinson's disease, and potentially, similar alterations occur in humans. (2) Genetic mutations of Netrin-1 receptors increase an individuals' susceptibility to neurodegenerative disorders. (3) Therapeutic approaches targeting Netrin-1 and its receptors offer the benefits of enhancing memory and motor function. (4) Netrin-1 and its receptors show genetic and epigenetic alterations in a variety of cancers. These findings provide compelling evidence that Netrin-1 and its receptors are crucial targets in neurodegenerative diseases. Through a comprehensive review of Netrin-1 signaling pathways, our objective is to uncover potential therapeutic avenues for neurodegenerative disorders.
在神经元发育过程中,Netrin-1及其受体在诱导轴突生长和神经元迁移方面发挥着关键作用。它们的深远影响随后延伸至成年期,涵盖神经元存活和突触功能的维持。越来越多的证据突出了几个关键点:(1)Netrin-1水平降低会加剧阿尔茨海默病和帕金森病动物模型中的病理进展,并且在人类中可能也会出现类似的改变。(2)Netrin-1受体的基因突变会增加个体对神经退行性疾病的易感性。(3)针对Netrin-1及其受体的治疗方法具有增强记忆和运动功能的益处。(4)Netrin-1及其受体在多种癌症中表现出基因和表观遗传改变。这些发现提供了令人信服的证据,表明Netrin-1及其受体是神经退行性疾病的关键靶点。通过对Netrin-1信号通路的全面综述,我们的目标是揭示神经退行性疾病潜在的治疗途径。