Department of Pharmacology, School of Health Sciences, Central University of Punjab, Ghudda, Bathinda 151401, Punjab, India.
Department of Pharmacology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India.
Life Sci. 2023 Oct 1;330:121983. doi: 10.1016/j.lfs.2023.121983. Epub 2023 Jul 29.
Alzheimer's disease (AD) is a progressive neurodegenerative condition that leads to memory loss and cognitive impairment over time. It is characterized by protein misfolding as well as prolonged cellular stress, such as perturbing calcium homeostasis and redox management. Numerous investigations have proven that endoplasmic reticulum failure may exhibit exacerbation of AD pathogenesis in AD patients, in-vivo and in-vitro models. The endoplasmic reticulum (ER) participates in a variety of biological functions including folding of protein, quality control, cholesterol production, and maintenance of calcium balance. A diverse range of physiological, pathological and pharmacological substances can interfere with ER activity and thus lead to exaggeration of ER stress. The unfolded protein response (UPR), an intracellular signaling network is stimulated due to ER stress. Three stress sensors found in the endoplasmic reticulum, the PERK, ATF6, and IRE1 transducers detect protein misfolding in the ER and trigger UPR, a complex system to maintain homeostasis. ER stress is linked to many of the major pathological processes that are seen in AD, including presenilin1 and 2 (PS1 and PS2) gene mutation, tau phosphorylation and β-amyloid formation. The role of ER stress and UPR in the pathophysiology of AD implies that they can be employed as potent therapeutic target. This study shows the relationship between ER and AD and how the pathogenesis of AD is influenced by the impact of ER stress. An effective method for the prevention or treatment of AD may involve therapeutic strategies that modify ER stress pathways.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，随着时间的推移会导致记忆丧失和认知障碍。它的特征是蛋白质错误折叠以及细胞应激的延长，例如破坏钙稳态和氧化还原管理。大量研究已经证明，内质网衰竭可能会加剧 AD 患者、体内和体外模型中的 AD 发病机制。内质网（ER）参与多种生物功能，包括蛋白质折叠、质量控制、胆固醇生成和钙平衡维持。各种生理、病理和药理学物质都可以干扰 ER 活性，从而导致 ER 应激的加剧。未折叠蛋白反应（UPR）是一种细胞内信号网络，由于 ER 应激而被激活。内质网中发现的三种应激传感器，PERK、ATF6 和 IRE1 转导器，检测 ER 中的蛋白质错误折叠，并触发 UPR，这是一个维持内稳态的复杂系统。ER 应激与 AD 中看到的许多主要病理过程有关，包括早老素 1 和 2（PS1 和 PS2）基因突变、tau 磷酸化和 β-淀粉样蛋白形成。ER 应激和 UPR 在 AD 病理生理学中的作用意味着它们可以作为有效的治疗靶点。本研究显示了 ER 与 AD 之间的关系，以及 ER 应激如何影响 AD 的发病机制。预防或治疗 AD 的有效方法可能涉及改变 ER 应激途径的治疗策略。
