Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability.
Exendin-4 antagonizes Aβ1-42-induced attenuation of spatial learning and memory ability.
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DOI：
10.3892/etm.2016.3742
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发表时间：
2016-11
影响因子：
2.7
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Wang X;Wang L;Jiang R;Xu Y;Zhao X;Li Y
β-淀粉样蛋白（Aβ）在参与认知和记忆的大脑中枢的积聚是阿尔茨海默病（AD）的关键病理特征。2型糖尿病（T2 DM）的发病过程与AD有许多相似之处。因此，假设用于治疗T2 DM的药物治疗可能有助于预防和改善AD症状。本研究证明，Exendin-4（一种胰高血糖素样肽-1类似物，用作T2 DM的治疗药物）可显著拮抗Aβ片段诱导的空间学习和记忆能力衰减，如Morris水迷宫实验所示。此外，我们研究了潜在的电生理和分子机制。结果表明，Exendin-4可在体内挽救Aβ1-42诱导的大鼠海马CA 1区长时程增强，并可拮抗Aβ1-42诱导的大鼠海马组织环磷酸腺苷和磷酸化cAMP反应元件结合蛋白的减少。本研究结果为Exendin-4改善AD提供了理论支持。
β-amyloid protein (Aβ) accumulation in cerebral centers involved in cognition and memory is a pivotal pathological feature of Alzheimer's disease (AD). The onset process of type 2 diabetes mellitus (T2DM) has a number of similarities compared with AD. Thus, it is hypothesized that the pharmacological therapy employed for the treatment of T2DM may help to prevent and ameliorate the symptoms of AD. This study demonstrated that Exendin-4, which is a glucagon-like peptide-1 analogue which is used as a therapeutic drug for T2DM, markedly antagonized Aβ fragment-induced attenuation of spatial learning and memory ability, as indicated by a Morris water maze experiment. In addition, we investigated the potential underlying electrophysiological and molecular mechanisms. The results indicate that Exendin-4 rescued long-term potentiation from Aβ1-42-induced damage in the rat hippocampal CA1 region in vivo, and antagonized Aβ1-42-induced reduction of cyclic adenosine monophosphate and phosphorylated-cAMP response element-binding protein in rat hippocampal tissue using ELISA and western blot analysis, respectively. Thus, the results of the present study provide theoretical support for the application of Exendin-4 for improving AD.
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影响因子：
15.1
作者：
Frank-Cannon TC;Alto LT;McAlpine FE;Tansey MG
通讯作者：
Tansey MG
DOI：
10.1016/s0140-6736(20)32205-4
发表时间：
2021-04-24
期刊：
Lancet (London, England)
影响因子：
--
作者：
Scheltens P;De Strooper B;Kivipelto M;Holstege H;Chételat G;Teunissen CE;Cummings J;van der Flier WM
通讯作者：
van der Flier WM
DOI：
10.1016/s0006-291x(84)80190-4
发表时间：
1984-01-01
影响因子：
3.1
作者：
GLENNER, GG;WONG, CW
通讯作者：
WONG, CW
影响因子：
64.8
作者：
Kahn, Steven E.;Hull, Rebecca L.;Utzschneider, Kristina M.
通讯作者：
Utzschneider, Kristina M.
影响因子：
7.7
作者：
Janson, J;Laedtke, T;Butler, PC
通讯作者：
Butler, PC