用于治疗阿尔茨海默病的小分子JNK3抑制剂的最新进展

Recent advances of small molecule JNK3 inhibitors for Alzheimer's disease.

作者信息

Qin Pengxia, Ran Yingying, Liu Yujing, Wei Chao, Luan Xiaoyi, Niu Haoqian, Peng Jie, Sun Jie, Wu Jingde

机构信息

Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, PR China.

出版信息

Bioorg Chem. 2022 Nov;128:106090. doi: 10.1016/j.bioorg.2022.106090. Epub 2022 Aug 9.

DOI:10.1016/j.bioorg.2022.106090

PMID:35964505

Abstract

C-Jun N-terminal kinase (JNK) is a member of mitogen-activated protein kinases (MAPKs) family, with three isoforms, JNK1, JNK2 and JNK3. Alzheimer's disease (AD) is a neurological disorder and the most common type of dementia. Two well-established AD pathologies are the deposition of Aβ amyloid plaques and neurofibrillary tangles caused by Tau hyperphosphorylation. JNK3 is involved in forming amyloid Aβ and neurofibrillary tangles, suggesting that JNK3 may represent a target to develop treatments for AD. Therefore, this review will discuss the roles of JNK3 in the pathogenesis and treatment of AD, and the latest progress in the development of JNK3 inhibitors.

摘要

c-Jun氨基末端激酶（JNK）是丝裂原活化蛋白激酶（MAPK）家族的成员，有三种亚型，即JNK1、JNK2和JNK3。阿尔茨海默病（AD）是一种神经疾病，也是最常见的痴呆类型。两种公认的AD病理特征是Aβ淀粉样斑块的沉积以及由Tau蛋白过度磷酸化导致的神经纤维缠结。JNK3参与Aβ淀粉样蛋白和神经纤维缠结的形成，这表明JNK3可能是开发AD治疗方法的一个靶点。因此，本综述将讨论JNK3在AD发病机制和治疗中的作用，以及JNK3抑制剂开发的最新进展。