Pin1在神经退行性疾病中的分子机制  

The molecular mechanism of peptidylprolyl cis/trans isomerase,NIMA-interacting 1 in neurodegenerative diseases

作　　者：邱丹[1] 魏倩萍[1] QIU Dan;WEI Qianping(The First Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China)

机构地区：[1]重庆医科大学第一附属医院,重庆400010

出　　处：《国际神经病学神经外科学杂志》2023年第2期67-70,共4页Journal of International Neurology and Neurosurgery

基　　金：重庆市自然科学基金面上项目(cstc2019jcyj-msxm0341)。

摘　　要：Pin1(peptidylprolyl cis/trans isomerase NIMA-interacting 1)为脯氨酸肽酶异构酶的亚类,是一种催化蛋白质中磷酸化丝氨酸(苏氨酸)―脯氨酸基序之间的肽键异构化酶,具有调节蛋白质折叠、细胞内信号转导、转录、细胞凋亡等功能。Pin1在中枢和周围神经系统中广泛表达,可调节各种神经元发育、凋亡和突触活动。尽管有研究报道,Pin1与神经元底物相互作用影响特定的信号通路,但在神经元水平的生物学功能仍缺乏更全面的了解。此外,越来越多的证据表明,Pin1在衰老及与年龄相关的神经退行性疾病(包括阿尔茨海默病、帕金森病、额颞痴呆、亨廷顿病和肌萎缩侧索硬化)中发挥着至关重要的作用,在这些疾病中,其介导了从神经保护到神经毒性的截然不同的作用。因此,进一步研究Pin1在神经元中的生物学功能,明确Pin1在年龄相关和神经退行性疾病中的分子机制,可为临床治疗相关疾病提供分子靶点。Peptidylprolyl cis/trans isomerase,NIMA-interacting 1(Pin1) is a peptide bond isomerase that catalyzes the phosphorylation of serine(threonine)-proline motifs in proteins and has the functions of regulating protein folding,intracellular signal transduction,transcription,and cell apoptosis.Pin1 is widely expressed in the central and peripheral nervous systems and can regulate the development,apoptosis,and synaptic activity of various neurons.Although studies have reported that Pin1 interacts with neuronal substrates to affect specific signaling pathways,there is still a lack of comprehensive understanding of its biological function at the neuronal level.In addition,an increasing amount of evidence has shown that Pin1 plays a crucial role in aging and age-related neurodegenerative diseases,including Alzheimer′s disease,Parkinson′s disease,frontotemporal dementia,Huntington′s disease,and amyotrophic lateral sclerosis,in which it mediates various roles from neuroprotection to neurotoxicity.Therefore,further studies are needed to investigate the biological function of Pin1 in neurons and clarify the molecular mechanism of Pin1 in age-related and neurodegenerative diseases,so as to provide molecular targets for the clinical treatment of related diseases.

关 键 词：神经退行性疾病 PIN1 异构化酶 

分 类 号：R741[医药卫生—神经病学与精神病学]