The inhibition of ORMDL3 prevents Alzheimer's disease through ferroptosis by PERK/ATF4/HSPA5 pathway

IF 3.8 4区工程技术 Q1 BIOCHEMICAL RESEARCH METHODS IET nanobiotechnology Pub Date : 2023-01-20 DOI:10.1049/nbt2.12113

Yankun Shao, Yilin Xu, Huang Di, Xinxiu Shi, Yingying Wang, Hongyu Liu, Lina Song

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引用次数: 2

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease with high incidence and widespread attention. There is currently no clear clarification of the pathogenesis. However, ORMDL3 causes ferroptosis in AD, and the potential mechanisms remain unclear. So, this study explore the function of ORMDL3 on ferroptosis in AD and its potential regulatory mechanisms. APPswe/PS1dE9 mice and C57BL/6 mice were induced into the mice model. The murine microglial BV-2 cells also were induced into the vitro model. In serum samples of AD patients, ORMDL3 mRNA expression levels were upregulated. The serum ORMDL3 levels expression was positively related to the ADL score or MoCA score in AD patients. The serum ORMDL3 expression level was positively related to MMSE score or Hcy levels in AD patients. The mRNA expression of ORMDL3 in the hippocampal tissue of the mice model of AD was upregulated at one, four and eight months. The protein expression of ORMDL3 was upregulated in the mice model of AD. ORMDL3 promoted Alzheimer's disease, and increased oxidative response and ferroptosis in a model of AD. PERK/ATF4/HSPA5 pathway is one important signal pathway for the effects of ORMDL3 in a model of AD. Collectively, these data suggested that ORMDL3 promoted oxidative response and ferroptosis in a model of AD by the PERK/ATF4/HSPA5 pathway, which might be a novel target spot mechanism of ferroptosis in AD and may serve as a regulator of AD-induced ferroptosis.

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ORMDL3通过PERK/ATF4/HSPA5途径抑制铁下垂预防阿尔茨海默病

阿尔茨海默病(Alzheimer's disease, AD)是一种发病率高、受到广泛关注的神经退行性疾病。目前还没有明确的发病机制。然而，ORMDL3导致AD中的铁下垂，其潜在机制尚不清楚。因此，本研究探讨ORMDL3在AD患者铁下垂中的作用及其可能的调控机制。将APPswe/PS1dE9小鼠和C57BL/6小鼠分别诱导成小鼠模型。小鼠小胶质细胞BV-2也被诱导成体外模型。在AD患者的血清样本中，ORMDL3 mRNA表达水平上调。AD患者血清ORMDL3水平表达与ADL评分或MoCA评分呈正相关。AD患者血清ORMDL3表达水平与MMSE评分或Hcy水平呈正相关。在1个月、4个月和8个月时，AD模型小鼠海马组织中ORMDL3 mRNA表达上调。ORMDL3蛋白在AD小鼠模型中表达上调。ORMDL3促进阿尔茨海默病，并增加AD模型中的氧化反应和铁吊。PERK/ATF4/HSPA5通路是ORMDL3在AD模型中发挥作用的重要信号通路。综上所述，这些数据表明ORMDL3通过PERK/ATF4/HSPA5途径促进AD模型中的氧化反应和铁下垂，这可能是AD中铁下垂的一种新的靶点机制，可能是AD诱导的铁下垂的调节剂。

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来源期刊

IET nanobiotechnology 工程技术-纳米科技

CiteScore

6.20

自引率

4.30%

发文量

审稿时长

1 months

期刊介绍： Electrical and electronic engineers have a long and illustrious history of contributing new theories and technologies to the biomedical sciences. This includes the cable theory for understanding the transmission of electrical signals in nerve axons and muscle fibres; dielectric techniques that advanced the understanding of cell membrane structures and membrane ion channels; electron and atomic force microscopy for investigating cells at the molecular level. Other engineering disciplines, along with contributions from the biological, chemical, materials and physical sciences, continue to provide groundbreaking contributions to this subject at the molecular and submolecular level. Our subject now extends from single molecule measurements using scanning probe techniques, through to interactions between cells and microstructures, micro- and nano-fluidics, and aspects of lab-on-chip technologies. The primary aim of IET Nanobiotechnology is to provide a vital resource for academic and industrial researchers operating in this exciting cross-disciplinary activity. We can only achieve this by publishing cutting edge research papers and expert review articles from the international engineering and scientific community. To attract such contributions we will exercise a commitment to our authors by ensuring that their manuscripts receive rapid constructive peer opinions and feedback across interdisciplinary boundaries. IET Nanobiotechnology covers all aspects of research and emerging technologies including, but not limited to: Fundamental theories and concepts applied to biomedical-related devices and methods at the micro- and nano-scale (including methods that employ electrokinetic, electrohydrodynamic, and optical trapping techniques) Micromachining and microfabrication tools and techniques applied to the top-down approach to nanobiotechnology Nanomachining and nanofabrication tools and techniques directed towards biomedical and biotechnological applications (e.g. applications of atomic force microscopy, scanning probe microscopy and related tools) Colloid chemistry applied to nanobiotechnology (e.g. cosmetics, suntan lotions, bio-active nanoparticles) Biosynthesis (also known as green synthesis) of nanoparticles; to be considered for publication, research papers in this area must be directed principally towards biomedical research and especially if they encompass in vivo models or proofs of concept. We welcome papers that are application-orientated or offer new concepts of substantial biomedical importance Techniques for probing cell physiology, cell adhesion sites and cell-cell communication Molecular self-assembly, including concepts of supramolecular chemistry, molecular recognition, and DNA nanotechnology Societal issues such as health and the environment Special issues. Call for papers: Smart Nanobiosensors for Next-generation Biomedical Applications - https://digital-library.theiet.org/files/IET_NBT_CFP_SNNBA.pdf Selected extended papers from the International conference of the 19th Asian BioCeramic Symposium - https://digital-library.theiet.org/files/IET_NBT_CFP_ABS.pdf