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c-Jun氨基末端激酶抑制剂作为阿尔茨海默病治疗药物的发展前景:通过对接研究探究其结构

A Perspective on the Development of c-Jun N-terminal Kinase Inhibitors as Therapeutics for Alzheimer's Disease: Investigating Structure through Docking Studies.

作者信息

Cho Hyunwook, Hah Jung-Mi

机构信息

Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan 15588, Korea.

Center for Proteinopathy, Institute of Pharmaceutical Science and Technology, Hanyang University, Ansan 15588, Korea.

出版信息

Biomedicines. 2021 Oct 9;9(10):1431. doi: 10.3390/biomedicines9101431.

Abstract

c-Jun N-terminal kinase (JNK) plays an important role in cell death caused by various stimuli. Because the isoform JNK3 is mainly expressed in the brain, it is believed to play a pivotal role in various neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), which still lack plausible therapeutics. To develop a novel and selective JNK3 inhibitor, we conducted a decadal review (2011 to 2021) of published articles on JNK inhibitors, particularly those focusing on a structural perspective and docking insights. We observed the structures of three isoforms of JNK, namely holo-proteins and co-crystal structures, with JNK3 inhibitors and summarized the significant structural aspects of selective JNK3 inhibitors as AD therapeutics.

摘要

c-Jun氨基末端激酶(JNK)在各种刺激引起的细胞死亡中起重要作用。由于JNK3亚型主要在大脑中表达,因此人们认为它在包括阿尔茨海默病(AD)和帕金森病(PD)在内的各种神经退行性疾病中起关键作用,而这些疾病仍然缺乏合理的治疗方法。为了开发一种新型的选择性JNK3抑制剂,我们对已发表的关于JNK抑制剂的文章进行了十年回顾(2011年至2021年),特别是那些从结构角度和对接见解方面进行研究的文章。我们观察了JNK三种亚型的结构,即全蛋白结构和与JNK3抑制剂的共晶体结构,并总结了作为AD治疗药物的选择性JNK3抑制剂的重要结构方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/15fe/8533360/2fd6e9c0f6d9/biomedicines-09-01431-g001.jpg

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