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Nurr1作为阿尔茨海默病相关发病机制的介导因子和治疗靶点的关键作用。

The Critical Role of Nurr1 as a Mediator and Therapeutic Target in Alzheimer's Disease-related Pathogenesis.

作者信息

Jeon Seong Gak, Yoo Anji, Chun Dong Wook, Hong Sang Bum, Chung Hyunju, Kim Jin-Il, Moon Minho

机构信息

1Department of Biochemistry, College of Medicine, Konyang University, Daejeon, 35365, Republic of Korea.

2Department of Core Research Laboratory, Clinical Research Institute, Kyung Hee University Hospital at Gangdong, Seoul 05278, Republic of Korea.

出版信息

Aging Dis. 2020 May 9;11(3):705-724. doi: 10.14336/AD.2019.0718. eCollection 2020 May.

Abstract

Several studies have revealed that the transcription factor nuclear receptor related 1 (Nurr1) plays several roles not only in the regulation of gene expression related to dopamine synthesis, but also in alternative splicing, and miRNA targeting. Moreover, it regulates cognitive functions and protects against inflammation-induced neuronal death. In particular, the role of Nurr1 in the pathogenesis of Parkinson's disease (PD) has been well investigated; for example, it has been shown that it restores behavioral and histological impairments in PD models. Although many studies have evaluated the connection between Nurr1 and PD pathogenesis, the role of Nurr1 in Alzheimer's disease (AD) remain to be studied. There have been several studies describing Nurr1 protein expression in the AD brain. However, only a few studies have examined the role of Nurr1 in the context of AD. Therefore, in this review, we highlight the overall effects of Nurr1 under the neuropathologic conditions related to AD. Furthermore, we suggest the possibility of using Nurr1 as a therapeutic target for AD or other neurodegenerative disorders.

摘要

多项研究表明,转录因子核受体相关蛋白1(Nurr1)不仅在与多巴胺合成相关的基因表达调控中发挥多种作用,还在可变剪接和微小RNA靶向作用中发挥作用。此外,它还调节认知功能并预防炎症诱导的神经元死亡。特别是,Nurr1在帕金森病(PD)发病机制中的作用已得到充分研究;例如,已表明它可恢复PD模型中的行为和组织学损伤。尽管许多研究评估了Nurr1与PD发病机制之间的联系,但Nurr1在阿尔茨海默病(AD)中的作用仍有待研究。已有多项研究描述了AD大脑中Nurr1蛋白的表达情况。然而,只有少数研究在AD背景下研究了Nurr1的作用。因此,在本综述中,我们重点介绍了Nurr1在与AD相关的神经病理条件下的总体作用。此外,我们提出了将Nurr1用作AD或其他神经退行性疾病治疗靶点的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9346/7220289/e4186e6fdf1a/ad-11-3-705-g1.jpg

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