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聚(ADP-核糖)聚合酶1(PARP1)在神经退行性疾病和衰老中的作用。

The role of PARP1 in neurodegenerative diseases and aging.

作者信息

Mao Kanmin, Zhang Guo

机构信息

Key Laboratory of Environmental Health, Ministry of Education, Department of Toxicology, School of Public Health, Tongji Medical College, Wuhan, China.

Institute for Brain Research, Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan, China.

出版信息

FEBS J. 2022 Apr;289(8):2013-2024. doi: 10.1111/febs.15716. Epub 2021 Feb 8.

Abstract

Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by progressive memory loss and motor impairment. Aging is a major risk factor for neurodegenerative diseases. Neurodegenerative diseases and aging often develop in an irreversible manner and cause a significant socioeconomic burden. When considering their pathogenesis, many studies usually focus on mitochondrial dysfunction and DNA damage. More recently, neuroinflammation, autophagy dysregulation, and SIRT1 inactivation were shown to be involved in the pathogenesis of neurodegenerative diseases and aging. In addition, studies uncovered the role of poly (ADP-ribose)-polymerase-1 (PARP1) in neurodegenerative diseases and aging. PARP1 links to a cluster of stress signals, including those originated by inflammation and autophagy dysregulation. In this review, we summarized the recent research progresses on PARP1 in neurodegenerative diseases and aging, with an emphasis on the relationship among PARP1, neuroinflammation, mitochondria, and autophagy. We discussed the possibilities of treating neurodegenerative diseases and aging through targeting PARP1.

摘要

神经退行性疾病,包括阿尔茨海默病(AD)和帕金森病(PD),其特征是进行性记忆丧失和运动障碍。衰老是神经退行性疾病的主要危险因素。神经退行性疾病和衰老通常以不可逆的方式发展,并造成重大的社会经济负担。在考虑其发病机制时,许多研究通常集中在线粒体功能障碍和DNA损伤上。最近,神经炎症、自噬失调和SIRT1失活被证明与神经退行性疾病和衰老的发病机制有关。此外,研究还揭示了聚(ADP-核糖)聚合酶-1(PARP1)在神经退行性疾病和衰老中的作用。PARP1与一系列应激信号相关联,包括那些由炎症和自噬失调引发的信号。在本综述中,我们总结了PARP1在神经退行性疾病和衰老方面的最新研究进展,重点关注PARP1、神经炎症、线粒体和自噬之间的关系。我们讨论了通过靶向PARP1治疗神经退行性疾病和衰老的可能性。

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