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浙江大学学报（医学版）
浙江大学学报（医学版）  2020, Vol. 49 Issue (1): 100-106    DOI: 10.3785/j.issn.1008-9292.2020.02.10
综述     
多腺苷二磷酸核糖基化修饰与神经退行性变性疾病
王毅(),卢韵碧*()
浙江大学医学院基础医学院药理学系, 浙江 杭州 310058
Poly adenosine diphosphate-ribosylation and neurodegenerative diseases
WANG Yi(),LU Yunbi*()
Department of Pharmacology, College of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou 310058, China
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摘要：

神经退行性疾病的发病率越来越高，但其治疗手段有限。多腺苷二磷酸核糖基化修饰（PARylation）是由多腺苷二磷酸核糖聚合酶（PARP）催化的蛋白质翻译后修饰。PARylation通过影响蛋白质在细胞内的移位、聚集、蛋白质活性和细胞死亡，参与脑卒中、帕金森病、阿尔茨海默病、运动神经元病等神经退行性变性疾病的发生和发展。PARP抑制剂通过抑制蛋白PARylation，在药物临床前试验和临床试验Ⅰ期都展现了明显的神经保护作用。然而，寻找作用更特异的、符合神经退行性变性疾病治疗药动学特点的新型PARP抑制剂，将是抗神经退行性药物研发的新方向。本文就PARylation与神经退行性变性疾病的研究进展作一综述。
关键词： 多聚ADP-核糖化作用;  聚ADP核糖聚合酶类;  神经退行性疾病;  酶抑制剂/治疗;  综述    
Abstract:

The morbidity of neurodegenerative diseases are increased in recent years, however, the treatment is limited. Poly ADP-ribosylation (PARylation) is a post-translational modification of protein that catalyzed by poly(ADP-ribose) polymerase (PARP). Studies have shown that PARylation is involved in many neurodegenerative diseases such as stroke, Parkinson's diseases, Alzheimer's disease, amyotrophic lateral sclerosis and so on, by affecting intracellular translocation of protein molecules, protein aggregation, protein activity, and cell death. PARP inhibitors have showed neuroprotective efficacy for neurodegenerative diseases in pre-clinical studies and phase Ⅰ clinical trials. To find new PARP inhibitors with more specific effects and specific pharmacokinetic characteristics will be the new direction for the treatment of neurodegenerative diseases. This paper reviews the recent progress on PARylation in neurodegenerative diseases.
Key words: Poly ADP ribosylation    Poly(ADP-ribose) polymerases    Neurodegeneration    Enzyme inhibitor/therapies    Review
收稿日期: 2019-09-05 出版日期: 2020-06-08
CLC:  R741  
基金资助: 浙江省自然科学基金(LY18H170001);浙江省医药卫生科技计划(2017KY320);浙江省教育厅一般科研项目(Y201636340)
通讯作者: 卢韵碧     E-mail: 182486@zju.edu.cn;yunbi@zju.edu.cn
作者简介: 王毅(1995-), 女, 硕士研究生, 主要从事药理学研究; E-mail:182486@zju.edu.cn; https://orcid.org/0000-0001-7628-1556
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引用本文:

王毅,卢韵碧. 多腺苷二磷酸核糖基化修饰与神经退行性变性疾病[J]. 浙江大学学报（医学版）, 2020, 49(1): 100-106.

WANG Yi,LU Yunbi. Poly adenosine diphosphate-ribosylation and neurodegenerative diseases. J Zhejiang Univ (Med Sci), 2020, 49(1): 100-106.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2020.02.10    或    http://www.zjujournals.com/med/CN/Y2020/V49/I1/100

图 1  多腺苷二磷酸核糖基化修饰(PARylation)在神经退行性变性疾病中的作用
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