Zhang Tong, Musheshe Nshunge, van der Veen Christina H J T M, Kessels Helmut W, Dolga Amalia, De Deyn Peter, Eisel Ulrich, Schmidt Martina
Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands.
Department of Molecular Neurobiology, Groningen Institute for Evolutionary Life Sciences, University of Groningen, 9747 AG Groningen, The Netherlands.
Biomedicines. 2023 Jul 25;11(8):2096. doi: 10.3390/biomedicines11082096.
Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by amyloid beta (Aβ) and hyperphosphorylated tau accumulation in the brain. Recent studies indicated that memory retrieval, rather than memory formation, was impaired in the early stage of AD. Our previous study reported that pharmacological activation of hippocampal Epac2 promoted memory retrieval in . A recent study suggested that pharmacological inhibition of Epac2 prevented synaptic potentiation mediated by GluA3-containing AMPARs. In this study, we aimed to investigate proteins associated with Epac2-mediated memory in hippocampal postmortem samples of AD patients and healthy controls compared with the experimental AD model and . Epac2 and phospho-Akt were downregulated in AD patients and , while Epac1 and phospho-ERK1/2 were not altered. GluA3 was reduced in and tended to decrease in AD patients. PSD95 tended to decrease in AD patients and . Interestingly, AKAP5 was increased in AD patients but not in , implicating its role in tau phosphorylation. Our study points to the downregulation of hippocampal expression of proteins associated with Epac2 in AD.
阿尔茨海默病（AD）是最常见的神经退行性疾病之一，其特征是大脑中β淀粉样蛋白（Aβ）和过度磷酸化的tau蛋白积累。最近的研究表明，在AD早期受损的是记忆提取，而非记忆形成。我们之前的研究报道，海马体中Epac2的药理学激活促进了记忆提取。最近的一项研究表明，对Epac2的药理学抑制可阻止由含GluA3的AMPA受体介导的突触增强。在本研究中，我们旨在调查与AD患者和健康对照者海马体死后样本中Epac2介导的记忆相关的蛋白质，并与实验性AD模型进行比较。在AD患者中，Epac2和磷酸化Akt表达下调，而Epac1和磷酸化ERK1/2未发生改变。在[具体模型或对象]中GluA3减少，在AD患者中则有减少趋势。在AD患者中，PSD95有减少趋势。有趣的是，AKAP5在AD患者中增加，但在[具体模型或对象]中未增加，这表明其在tau蛋白磷酸化中发挥作用。我们的研究指出了AD中与Epac2相关的海马体蛋白表达下调。
