Canadian International School, Singapore, Singapore 649414.
Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Biomed Res Int. 2022 Aug 31;2022:8804925. doi: 10.1155/2022/8804925. eCollection 2022.
Alzheimer's disease, a neurodegenerative memory disease, primarily results from the formation of amyloid plaques (A) that gradually inhibit neuron communications. The entire mechanism of A production remains unclear to date, and it is of particular interest among scientists to find out the exact mechanism that leads to amyloid precursor protein (APP) cleavage through the amyloidogenic pathway so that effective treatments can be developed.
2 sets of experiments with the use of human H4-N cell lines are proposed to fully investigate the validity of the hypothesis. All of the experiments would involve immunoblotting of A using an anti-A antibody, and the results would be analyzed with the assistance of an image analyzer. A significant amount of A would be expected to be present in the cytoplasm of cells with herpes simplex virus (HSV-1) applied, as APP endocytosis would be induced by HSV-1, which leads to higher A levels inside the cell.
In this paper, a new hypothesis is presented on how HSV-1 infection initiates APP endocytosis and causes an increase in APP cleavage and A production inside the cells. It is also hypothesized that increased A peptides exit the cell via exocytosis, therefore, leading to the development of Alzheimer's disease. The findings will support the hypothesis if intracellular A concentration is significantly higher after the introduction of dHSV-1 and subsequently if extracellular A concentration becomes higher without TeNT exocytosis inhibition.
The results of this study would provide valuable insights into the mechanisms underlying Alzheimer's disease and open new scopes of research for its potential treatments. Further studies on virus infection and the development of memory diseases should be conducted to investigate possible correlations.
阿尔茨海默病是一种神经退行性记忆疾病，主要由淀粉样斑块（A）的形成引起，这些斑块逐渐抑制神经元的通讯。到目前为止，A 的产生机制还不完全清楚，科学家们特别感兴趣的是找出导致淀粉样前体蛋白（APP）通过淀粉样形成途径裂解的确切机制，以便开发有效的治疗方法。
提出了两组使用人 H4-N 细胞系的实验，以充分验证该假说的有效性。所有实验都将涉及使用抗 A 抗体对 A 进行免疫印迹，并用图像分析仪对结果进行分析。预计应用单纯疱疹病毒（HSV-1）后，细胞内 A 会大量存在，因为 HSV-1 会诱导 APP 内吞作用，从而导致细胞内 A 水平升高。
本文提出了一个新的假说，即 HSV-1 感染如何引发 APP 内吞作用，并导致细胞内 APP 裂解和 A 生成增加。还假设增加的 A 肽通过胞吐作用离开细胞，因此导致阿尔茨海默病的发生。如果在引入 dHSV-1 后细胞内 A 浓度显著升高，并且如果没有 TeNT 胞吐作用抑制后细胞外 A 浓度升高，则支持该假说。
本研究的结果将为阿尔茨海默病的发病机制提供有价值的见解，并为其潜在治疗方法开辟新的研究领域。应该进一步研究病毒感染和记忆疾病的发展，以调查可能的相关性。
