Akyuz Enes, Villa Chiara, Beker Merve, Elibol Birsen
Department of Biophysics, Faculty of Medicine, Yozgat Bozok University, Yozgat 66100, Turkey.
School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy.
Biomedicines. 2020 Mar 13;8(3):58. doi: 10.3390/biomedicines8030058.
Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex etiology and characterized by cognitive deficits and memory loss. The pathogenesis of AD is not yet completely elucidated, and no curative treatment is currently available. Inwardly rectifying potassium (Kir) channels are important for playing a key role in maintaining the resting membrane potential and controlling cell excitability, being largely expressed in both excitable and non-excitable tissues, including neurons. Accordingly, the aim of the study is to investigate the role of neuronal Kir channels in AD pathophysiology. The mRNA and protein levels of neuronal Kir2.1, Kir3.1, and Kir6.2 were evaluated by real-time PCR and Western blot analysis from the hippocampus of an amyloid-β(Aβ)-infused rat model of AD. Extracellular deposition of Aβ was confirmed by both histological Congo red staining and immunofluorescence analysis. Significant decreased mRNA and protein levels of Kir2.1 and Kir6.2 channels were observed in the rat model of AD, whereas no differences were found in Kir3.1 channel levels as compared with controls. Our results provide in vivo evidence that Aβ can modulate the expression of these channels, which may represent novel potential therapeutic targets in the treatment of AD.
阿尔茨海默病（AD）是一种病因复杂的进行性神经退行性疾病，其特征为认知缺陷和记忆丧失。AD的发病机制尚未完全阐明，目前尚无治愈性治疗方法。内向整流钾（Kir）通道对于维持静息膜电位和控制细胞兴奋性起着关键作用，在包括神经元在内的可兴奋和不可兴奋组织中均大量表达。因此，本研究的目的是探讨神经元Kir通道在AD病理生理学中的作用。通过实时PCR和蛋白质印迹分析，评估了淀粉样β蛋白（Aβ）注入的AD大鼠模型海马中神经元Kir2.1、Kir3.1和Kir6.2的mRNA和蛋白质水平。通过组织学刚果红染色和免疫荧光分析证实了Aβ的细胞外沉积。在AD大鼠模型中观察到Kir2.1和Kir6.2通道的mRNA和蛋白质水平显著降低，而与对照组相比，Kir3.1通道水平未发现差异。我们的结果提供了体内证据，表明Aβ可以调节这些通道的表达，这可能代表了AD治疗中的新型潜在治疗靶点。
