肽基脯氨酰顺反异构酶Pin1在阿尔茨海默病发生发展中的作用
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西北工业大学,河北工程大学,中国科学院生物物理研究所

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国家自然科学基金(31200551),高等学校博士学科点专项科研基金(20126102120068),河北省高等学校科学技术研究项目(QN20131051),陕西省自然科学基础研究计划(2013JQ4032)和中央高校基本科研业务费专项资金(3102015ZY083)资助项目


The Role of the Peptidyl-Prolyl cis/trans Isomerase Pin1 in The Occurrence and Development of Alzheimer′s Disease
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Northwestern Polytechnical University,Hebei University of Engineering,Institute of Biophysics, Chinese Academy of Sciences

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This work was supported by grants from The National Natural Science Foundation of China (31200551), Specialized Research Fund for the Doctoral Program of Higher Education(20126102120068), Science and Technology Research Projects for Universities in Hebei of China (QN20131051), Natural Science Basic Research Plan in Shaanxi Province of China (2013JQ4032), and the Fundamental Research Funds for the Central Universities (3102015ZY083).

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    摘要:

    Pin1是目前发现的人体内唯一识别蛋白质中pSer/pThr-Pro的顺反异构酶,与阿尔茨海默病(Alzheimer′s disease,AD)的发生存在重要联系.Pin1调控AD相关分子的结构和功能,抑制神经纤维缠结、老年斑、脑血管淀粉样沉积等AD病理学特征,促进神经前体细胞分化成神经元,在一定程度上起到了阻止AD发生和发展的作用.同时,人体内Pin1功能紊乱可能是AD发生机制之一,尽管如此,Pin1能否成为预防和治疗AD的靶蛋白还有待临床验证.鉴于目前针对脑内单分子的AD药物疗效较差,联合Pin1与相关分子的“多靶点药物组合”可能是一种未来AD防治的研究策略.

    Abstract:

    Pin1 is the only known cis-trans isomerase that recognizes pThr/pSer-Pro in proteins, relevant to the pathogenesis of Alzheimer′s disease (AD). Pin1 regulates the structures and functions of some molecules that are related to AD, inhibits the main AD pathological characteristics such as neurofibrillary tangles (NFTs), senile plaques (SPs), and cerebral amyloid angiopathy (CAA), promotes the differentiation of neural progenitor cells (NPCs) to neurons, and to some extent prevents the occurrence and development of AD. Meanwhile, Pin1 dysfunction in vivo may be involved in the pathogenesis of AD. Nevertheless, whether Pin1 could be a therapeutic target for the prevention and treatment of AD still needs to be verified clinically. Considering of the poor efficacy of AD medicines that target each single molecule in brain, the "combined multiple-target medicine" focusing on Pin1 and other related molecules may be a therapeutic strategy for AD in the future.

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侯海,王敬章,李雪梅.肽基脯氨酰顺反异构酶Pin1在阿尔茨海默病发生发展中的作用[J].生物化学与生物物理进展,2015,42(5):434-442

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  • 收稿日期:2015-03-02
  • 最后修改日期:2015-03-27
  • 接受日期:2015-03-27
  • 在线发布日期: 2015-05-22
  • 出版日期: 2015-05-20
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