莫里斯水上航行任务
海马体
药理学
毒蕈碱乙酰胆碱受体
医学
乙酰胆碱
转基因小鼠
毒蕈碱乙酰胆碱受体M1
神经科学
病理
内分泌学
转基因
内科学
化学
生物
受体
生物化学
基因
作者
Ziyan Li,Kaili Jia,Yale Duan,Dong Wang,Zhou Zong-li,Dong Shen
出处
期刊:Molecular Medicine Reports
[Spandidos Publications]
日期:2017-05-01
卷期号:16 (5): 7835-7840
被引量:6
标识
DOI:10.3892/mmr.2017.7502
摘要
Agonists of M1 muscarinic acetylcholine receptors are promising therapeutic agents for the treatment of Alzheimer's disease (AD). An example of one of these agents is xanomeline, which has been a leading candidate, however induces various unwanted adverse effects. 3‑[3‑(3‑florophenyl‑2‑propyn‑1‑ylthio)‑1,2,5‑thiadiazol-4-yl]-1,2,5,6-tetrahydro‑1‑methylpyridine oxalate (EUK1001), a fluorinated derivative of xanomeline, has been demonstrated to attenuate AD‑like neurodegenerative pathology in presenilin‑deficient mice, which has no β‑amyloid (Aβ) pathology. The present study assessed the effect of EUK1001 on the behavioral performance of the 3xTg‑AD model of AD. EUK1001 treatment decreased cognitive deficits in male and female AD mice in the Morris water maze test and novel object recognition tasks. EUK1001 also decreased Aβ42, however not Aβ40 in the cortex and hippocampus of AD mice. EUK1001 may also alter amyloid precursor protein processing to a nonamyloidgenic pathway in vitro. These results demonstrate that EUK1001 may ameliorate the cognitive dysfunction of AD mice, possibly by reducing Aβ production. Therefore, EUK1001 may be an effective treatment for AD.
科研通智能强力驱动
Strongly Powered by AbleSci AI