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DW14006 as a Direct AMPK alpha Activator Ameliorates Diabetic Peripheral Neuropathy in Mice

文献类型：期刊论文

作者Xu, Xu2; Wang, Wei1,3; Wang, Zhengyu4; Lv, Jianlu2; Xu, Xiaoju2; Xu, Jiawen2; Yang, Juanzhen2; Zhu, Xialin2; Lu, Yin2; Duan, Wenhu1,3
刊名DIABETES
出版日期2020-09-01
卷号69期号:9页码:1974-1988
ISSN号0012-1797
DOI10.2337/db19-1084
通讯作者Wang, Jiaying(wangjy@njucm.edu.cn) ; Zhou, Jinpei(zhjp@cpu.edu.cn) ; Shen, Xu(xshen@njucm.edu.cn)
英文摘要Diabetic peripheral neuropathy (DPN) is a long-term complication of diabetes with a complicated pathogenesis. AMP-activated protein kinase (AMPK) senses oxidative stress, and mitochondrial function plays a central role in the regulation of DPN. Here, we reported that DW14006 (2-[3-(7-chloro-6-[2 '-hydroxy-(1,1 '-biphenyl)-4-yl]-2-oxo-1,2-dihydroquinolin-3-yl)phenyl]acetic acid) as a direct AMPK alpha activator efficiently ameliorated DPN in both streptozotocin (STZ)-induced type 1 and BKSdb/dbtype 2 diabetic mice. DW14006 administration highly enhanced neurite outgrowth of dorsal root ganglion neurons and improved neurological function in diabetic mice. The underlying mechanisms have been intensively investigated. DW14006 treatment improved mitochondrial bioenergetics profiles and restrained oxidative stress and inflammation in diabetic mice by targeting AMPK alpha, which has been verified by assay against the STZ-induced diabetic mice injected with adeno-associated virus 8-AMPK alpha-RNAi. To our knowledge, our work might be the first report on the amelioration of the direct AMPK alpha activator on DPN by counteracting multiple risk factors including mitochondrial dysfunction, oxidative stress, and inflammation, and DW14006 has been highlighted as a potential leading compound in the treatment of DPN.
WOS关键词ROOT GANGLIA NEURONS ; MITOCHONDRIAL DYSFUNCTION ; OXIDATIVE STRESS ; KINASE ; MECHANISMS ; BIOENERGETICS ; PATHOGENESIS ; ALLODYNIA ; GLUCOSE ; TARGET
资助项目National Science & Technology Major Project Key New Drug Creation and Manufacturing Program of China[2018ZX09711002] ; National Natural Science Foundation for Young Scientists of China[81703806] ; Postgraduate Research & Practice Innovation Program of Jiangsu Province[KYCX18_1600] ; Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica[JKLPSE201801] ; Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions(Integration of Chinese and Western Medicine)
WOS研究方向Endocrinology & Metabolism
语种英语
WOS记录号WOS:000560863400013
出版者AMER DIABETES ASSOC
源URL[http://119.78.100.183/handle/2S10ELR8/292339]  
专题中国科学院上海药物研究所
通讯作者Wang, Jiaying; Zhou, Jinpei; Shen, Xu
作者单位1.Univ Chinese Acad Sci, Beijing, Peoples R China
2.Nanjing Univ Chinese Med, Jiangsu Key Lab Pharmacol & Safety Evaluat Chines, Nanjing, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Medica, Dept Med Chem, Shanghai, Peoples R China
4.China Pharmaceut Univ, Dept Med Chem, Nanjing, Peoples R China
推荐引用方式
GB/T 7714		 Xu, Xu,Wang, Wei,Wang, Zhengyu,et al. DW14006 as a Direct AMPK alpha Activator Ameliorates Diabetic Peripheral Neuropathy in Mice[J]. DIABETES,2020,69(9):1974-1988.
APA Xu, Xu.,Wang, Wei.,Wang, Zhengyu.,Lv, Jianlu.,Xu, Xiaoju.,...&Shen, Xu.(2020).DW14006 as a Direct AMPK alpha Activator Ameliorates Diabetic Peripheral Neuropathy in Mice.DIABETES,69(9),1974-1988.
MLA Xu, Xu,et al."DW14006 as a Direct AMPK alpha Activator Ameliorates Diabetic Peripheral Neuropathy in Mice".DIABETES 69.9(2020):1974-1988.

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来源：上海药物研究所

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