Department of Neurology, Qilu Hospital of Shandong University and Brain Science Research Institute, Shandong University, China; Department of Intensive Care Unit, Jinan Central Hospital Affiliated to Shandong University, China.
Department of Rehabilitation, Qilu Hospital of Shandong University, China.
Biochem Biophys Res Commun. 2020 Apr 16;524(4):1057-1063. doi: 10.1016/j.bbrc.2020.02.036. Epub 2020 Feb 15.
Adherens junction-associated protein-1 (AJAP1), also called SHREW1, was first discovered as a novel component of adherens junctions in 2004. In later studies, AJAP1 was found to suppress invasion and predict recurrence of some tumors. Apart from its function as a putative tumor suppressor, AJAP1 is still poorly understood. Schwenk et al. recently found that AJAP1 was tightly associated with the γ-Aminobutyric acid type B receptor subunit 1(GABAR1). It is well known that GABAR plays a vital role in epilepsy as an inhibitory transmitter receptor. Structurally adjacent, possibly functionally interacting, therefore, we hypothesize that AJAP1 participates in the onset and progression of epilepsy. We designed this experiment to investigate the expression and location of AJAP1 in temporal lobe epilepsy (TLE) patients and kainic acid(KA)-induced epilepsy animal models by immunofluorescence and Western blot analyses. We overexpressed and inhibited AJAP1 through lentiviruses in KA-induced models and observed the corresponding effects on epileptic animals. Double-label immunofluorescence showed that AJAP1 was expressed mainly in neurons. Western blot analysis revealed that AJAP1 expression was downregulated in the neocortex of TLE patients and the hippocampus and neocortex of epileptic animal models. The overexpression of AJAP1 can reduce the frequency of spontaneous seizures, whereas the inhibition of AJAP1 expression can increase the incidence rate. Our study demonstrated that AJAP1 may be involved in the pathogenic process of epilepsy and may represent a novel antiepileptic target.
黏着斑相关蛋白-1（AJAP1），也称为 SHREW1，于 2004 年首次被发现作为黏着斑的一种新型组成部分。在后来的研究中，AJAP1 被发现抑制侵袭，并预测一些肿瘤的复发。除了作为潜在的肿瘤抑制因子的功能外，AJAP1 仍然知之甚少。Schwenk 等人最近发现 AJAP1 与γ-氨基丁酸 B 型受体亚基 1（GABAR1）紧密相关。众所周知，GABAR 作为抑制性递质受体在癫痫中起着至关重要的作用。结构上相邻，可能具有功能相互作用，因此，我们假设 AJAP1 参与癫痫的发生和进展。我们设计了这项实验，通过免疫荧光和 Western blot 分析来研究 AJAP1 在颞叶癫痫（TLE）患者和海人酸（KA）诱导的癫痫动物模型中的表达和定位。我们通过慢病毒在 KA 诱导的模型中过表达和抑制 AJAP1，并观察对癫痫动物的相应影响。双标免疫荧光显示 AJAP1 主要表达在神经元中。Western blot 分析显示，TLE 患者的新皮层和癫痫动物模型的海马和新皮层中 AJAP1 的表达下调。AJAP1 的过表达可以降低自发性癫痫发作的频率，而 AJAP1 表达的抑制可以增加发生率。我们的研究表明，AJAP1 可能参与癫痫的发病过程，可能代表一种新的抗癫痫靶点。
