Discovery of an evodiamine derivative for PI3K/AKT/GSK3β pathway activation and AD pathology improvement in mouse models.
Discovery of an evodiamine derivative for PI3K/AKT/GSK3β pathway activation and AD pathology improvement in mouse models.
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在小鼠模型中发现用于PI 3 K/AKT/GSK 3 β通路活化和AD病理学改善的吴茱萸碱衍生物。
DOI：
10.3389/fnmol.2022.1025066
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发表时间：
2022
影响因子：
4.8
通讯作者：
Zhang, Lianfeng
中科院分区：
文献类型：
--
作者：
Pang, Shuo;Li, Siyuan;Cheng, Hanzeng;Luo, Zhuohui;Qi, Xiaolong;Guan, Feifei;Dong, Wei;Gao, Shan;Liu, Ning;Gao, Xiang;Pan, Shuo;Zhang, Xu;Zhang, Li;Yang, Yajun;Zhang, Lianfeng
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive neurodegeneration and cognitive decline. Evodiamine, a main component in Chinese medicine, was found to improve cognitive impairment in AD model mice based on several intensive studies. However, evodiamine has high cytotoxicity and poor bioactivity. In this study, several evodiamine derivatives were synthesized via heterocyclic substitution and amide introduction and screened for cytotoxicity and antioxidant capacity. Under the same concentrations, compound 4c was found to exhibit lower cytotoxicity and higher activity against H2O2 and amyloid β oligomers (AβOs) than evodiamine in vitro and significantly improve the working memory and spatial memory of 3 x Tg and APP/PS1 AD mice. Subsequent RNA sequencing and pathway enrichment analysis showed that 4c affected AD-related genes and the AMPK and insulin signaling pathways. Furthermore, we confirmed that 4c recovered PI3K/AKT/GSK3β/Tau dysfunction in vivo and in vitro. In conclusion, 4c represents a potential lead compound for AD therapy based on the recovery of PI3K/AKT/GSK3β pathway dysfunction.
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DOI：
10.1186/alzrt265
发表时间：
2014
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Kitagishi Y;Nakanishi A;Ogura Y;Matsuda S
通讯作者：
Matsuda S
影响因子：
15.1
作者：
Querfurth H;Lee HK
通讯作者：
Lee HK
DOI：
10.1016/j.jalz.2018.01.015
发表时间：
2018-05
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Chiba-Falek O;Gottschalk WK;Lutz MW
通讯作者：
Lutz MW
DOI：
10.3233/jad-170490
发表时间：
2018
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Huber CM;Yee C;May T;Dhanala A;Mitchell CS
通讯作者：
Mitchell CS
影响因子：
5.6
作者：
Chou CH;Yang CR
通讯作者：
Yang CR