Klotho基因在神经变性病中的研究进展

Research progress of Klotho gene in neurodegenerative diseases

Klotho(Kl)是一种衰老抑制基因,其对CNS有保护作用,与神经变性疾病如Alzheimer’s病、帕金森病等具有明显的相关性。在Alzheimer’s病中,Kl对抗β淀粉样物质对海马神经元造成的损害,细胞层面上能显著改善长时程记忆基础中的N-甲基-D-天冬氨酸受体结构功能和网络反应敏感性,分子层面上能调节硫氧还蛋白/过氧化物酶氧化还原系统等的表达;对帕金森病,Kl负性调控维生素D合成以保护多巴胺能神经元,维持多巴胺的正常合成和分泌,这一过程主要是增强了信号调节激酶1、cAMP依赖性蛋白激酶A、钙/钙调素依赖激酶Ⅱ等信号的表达;Kl可以保护CNS免受氧化应激的损害。其他如肌萎缩侧索硬化及多系统萎缩等也受到Kl的保护,随着Kl研究的深入,未来有望成为治疗神经变性疾病的新途径。

Klotho(Kl) is an aging suppressor gene, which has a protective effect on the central nervous system. Klotho is closely related to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. In Alzheimer’s disease, Kl can resist the lesion caused by Aβ to hippocampal neurons. At the cellular level, Kl can significantly improve the structure and function of N-methyl-D-aspartate receptor and the sensitivity of network response in the basis of long-term memory. At the molecular level, it can regulate the expression of thioredoxin/peroxidase redox system. For Parkinson’s disease, Kl negatively regulates the synthesis of vitamin D to protect dopaminergic neurons and maintain the normal synthesis and secretion of dopamine. This process mainly increases the expression of signal regulated kinase 1, camp dependent protein kinase A and calcium/calmodulin dependent kinase Ⅱ and other signals. Kl can protect the central nervous system from oxidative stress. Other diseases such as amyotrophic lateral sclerosis and multiple system atrophy are also protected by Kl. With the further research of Kl, it is expected to become a new approach to treat neurodegenerative diseases in the future.